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Kinase and rheumatic disease

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https://www.readbyqxmd.com/read/28397126/protein-tyrosine-phosphatases-in-systemic-sclerosis-potential-pathogenic-players-and-therapeutic-targets
#1
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
#2
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...
April 7, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
February 27, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/27912150/calea-uniflora-less-attenuates-the-inflammatory-response-to-carrageenan-induced-pleurisy-in-mice
#9
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
https://www.readbyqxmd.com/read/27846303/auranofin-inhibits-retinal-pigment-epithelium-cell-survival-through-reactive-oxygen-species-dependent-epidermal-growth-factor-receptor-mitogen-activated-protein-kinase-signaling-pathway
#10
Xiaodong Chen, Radouil Tzekov, Mingyang Su, Haiyan Hong, Wang Min, Aidong Han, Wensheng Li
Abnormal survival of retinal pigment epithelium (RPE) cells contributes to the pathogenesis of proliferative vitreoretinopathy (PVR), a sight-threatening disease. In this study, we explored the effect of the anti-rheumatic agent auranofin (AF) on RPE cell survival and studied the underlying signaling mechanisms in vitro. Our results showed that AF inhibited ARPE-19 cell survival in a dose and time-dependent manner. Application of AF induced several effects: a significant decrease in total epidermal growth factor receptor (EGFR) and an increase in phosphorylated EGFR and mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), P38 mitogen-activated protein kinase (P38MAPK), c-Jun N-terminal kinase (JNK), c-Jun, mitogen activated protein kinase activated protein kinase 2(MAPKAPK2), and heat shock protein 27 (HSP27)...
2016: PloS One
https://www.readbyqxmd.com/read/27836567/management-of-psoriatic-arthritis-early-diagnosis-monitoring-of-disease-severity-and-cutting-edge-therapies
#11
REVIEW
Siba P Raychaudhuri, Reason Wilken, Andrea C Sukhov, Smriti K Raychaudhuri, Emanual Maverakis
Psoriatic arthritis (PsA) is a heterogeneous disease that can involve a variety of distinct anatomical sites including a patient's peripheral and axial joints, entheses, skin and nails. Appropriate management of PsA requires early diagnosis, monitoring of disease activity, and utilization of cutting edge therapies. To accomplish the former there are a variety of PsA-specific tools available to screen, diagnose, and assess patients. This review will outline the recently developed PsA screening tools, including the Toronto Psoriatic Arthritis Screening Questionnaire (TOPAS), the Psoriasis Epidemiology Screening Tool (PEST), the Psoriatic Arthritis Screening and Evaluation (PASE), and the Psoriasis and Arthritis Screening Questionnaire (PASQ)...
January 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27733572/neutrophil-biomarkers-predict-response-to-therapy-with-tumor-necrosis-factor-inhibitors-in-rheumatoid-arthritis
#12
Helen L Wright, Trevor Cox, Robert J Moots, Steven W Edwards
Neutrophils are implicated in the pathology of rheumatoid arthritis (RA), but the mechanisms regulating their activation are largely unknown. RA is a heterogeneous disease, and whereas many patients show clincal improvement during TNF inhibitor (TNFi) therapy, a significant proportion fails to respond. In vitro activation of neutrophils with agents, including TNF, results in rapid and selective changes in gene expression, but how neutrophils contribute to TNF signaling in RA and whether TNFi sensitivity involves differential neutrophil responses are unknown...
October 12, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27723271/baricitinib-methotrexate-or-combination-in-patients-with-rheumatoid-arthritis-and-no-or-limited-prior-disease-modifying-antirheumatic-drug-treatment
#13
Roy Fleischmann, Michael Schiff, Désirée van der Heijde, Cesar Ramos-Remus, Alberto Spindler, Marina Stanislav, Cristiano A F Zerbini, Sirel Gurbuz, Christina Dickson, Stephanie de Bono, Douglas Schlichting, Scott Beattie, Wen-Ling Kuo, Terence Rooney, William Macias, Tsutomu Takeuchi
OBJECTIVE: We undertook this phase III study to evaluate baricitinib, an orally administered JAK-1/JAK-2 inhibitor, as monotherapy or combined with methotrexate (MTX) compared to MTX monotherapy in patients with active rheumatoid arthritis (RA) who had received no or minimal conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and who were naive to biologic DMARDs. METHODS: A total of 588 patients were randomized 4:3:4 to receive MTX monotherapy (once weekly), baricitinib monotherapy (4 mg once daily), or the combination of baricitinib and MTX for 52 weeks...
March 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27690665/chemical-jak-inhibitors-for-the-treatment-of-rheumatoid-arthritis
#14
Shingo Nakayamada, Satoshi Kubo, Shigeru Iwata, Yoshiya Tanaka
Considerable advances in the treatment of rheumatoid arthritis (RA) have been made following the advent of biological disease-modifying anti-rheumatic drugs (DMARDs). However, biological DMARDs require intravenous or subcutaneous injection and some patients fail to respond to these drugs or lose their primary response. Currently, Janus kinase (JAK) inhibitors have been developed as a new class of DMARD that inhibits the non-receptor tyrosine kinase family JAK involved in intracellular signaling of various cytokines and growth factors...
October 3, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27584788/kinsenoside-screening-with-a-microfluidic-chip-attenuates-gouty-arthritis-through-inactivating-nf-%C3%AE%C2%BAb-signaling-in-macrophages-and-protecting-endothelial-cells
#15
Qiao Han, Wang Bing, Yin Di, Li Hua, Li Shi-He, Zheng Yu-Hua, Han Xiu-Guo, Wang Yu-Gang, Fan Qi-Ming, Yang Shih-Mo, Tang Ting-Ting
Gouty arthritis is a rheumatic disease that is characterized by the deposition of monosodium urate (MSU) in synovial joints cause by the increased serum hyperuricemia. This study used a three-dimensional (3D) flowing microfluidic chip to screen the effective candidate against MSU-stimulated human umbilical vein endothelial cell (HUVEC) damage, and found kinsenoside (Kin) to be the leading active component of Anoectochilus roxburghi, one of the Chinese medicinal plant widely used in the treatment of gouty arthritis clinically...
2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27577235/recent-progress-in-jak-inhibitors-for-the-treatment-of-rheumatoid-arthritis
#16
REVIEW
Shingo Nakayamada, Satoshi Kubo, Shigeru Iwata, Yoshiya Tanaka
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovial inflammation and joint destruction. Considerable advance in the treatment of RA has been made following the advent of biological disease-modifying anti-rheumatic drugs (DMARDs). However, these biologics require intravenous or subcutaneous injection and some patients fail to respond to biological DMARDs or lose their primary response. Various cytokines and cell surface molecules bind to receptors on the cell surface, resulting in the activation of various cell signaling pathways, including phosphorylation of kinase proteins...
October 2016: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/27569824/myocardial-protective-effects-of-l-carnitine-on-ischemia-reperfusion-injury-in-patients-with-rheumatic-valvular-heart-disease-undergoing-cardiac-surgery
#17
Ming Li, Li Xue, Haifeng Sun, Suochun Xu
OBJECTIVES: The authors used L-carnitine as an ingredient in cardioplegic solution during valve replacement surgery to investigate the protective effect of L-carnitine on myocardial ischemia-reperfusion injury (MIRI) and its possible mechanism. DESIGN: Prospective, randomized study. SETTING: A tertiary-care hospital. PARTICIPANTS: The study comprised 90 patients undergoing valve replacement under cardiopulmonary bypass...
December 2016: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/27550296/transforming-growth-factor-%C3%AE-activated-kinase-1-a-potential-therapeutic-target-for-rheumatic-diseases
#18
REVIEW
Sabrina Fechtner, David A Fox, Salahuddin Ahmed
Pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α are central regulators of autoinflammatory diseases. While targeting these cytokines has proven to be a successful clinical strategy, the long-term challenges such as drug resistance, lack of efficacy and poor clinical outcomes in some patients are some of the limitations faced by these therapies. This has ignited strategies to reduce inflammation by potentially targeting a variety of molecules, including cell surface receptors, signalling proteins and/or transcription factors to minimize cytokine-induced inflammation and tissue injury...
August 21, 2016: Rheumatology
https://www.readbyqxmd.com/read/27320933/relation-between-disease-modifying-anti-rheumatic-drugs-and-herpes-zoster-in-rheumatoid-arthritis
#19
REVIEW
Kunihiro Yamaoka
  Biologics have revolutionized the treatment of rheumatoid arthritis (RA). However certain amount of the patients cannot achieve goal of therapy. Recently, compounds targeting the intracellular kinase, Janus kinase (JAK) have demonstrated therapeutic effects resembling biologics. Tofacitinib is the only JAK inhibitor approved for RA and during the clinical trial, increased events of herpes zoster (HZ) was observed. Incidence rate was twice as much as patients treated with conventional anti-rheumatic drug and was especially increased in Japan that was four times as much...
2016: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/27311188/-tofacitinib-for-the-treatment-of-rheumatoid-arthritis
#20
REVIEW
Yoshiya Tanaka
The combined use of synthetic disease-modifying anti-rheumatic drugs (sDMARDs) such as methotrexate and biological DMARDs (bDMARDs) has revolutionized treatment of rheumatoid arthritis (RA). Remission is now realistic targets, achieved by a large proportion of RA patients. However, bDMARDs are limited to intravenous or subcutaneous uses and orally available small but strong products have been developed. Oral administration of tofacitinib targeting the Janus kinase (JAK) is significantly effective than placebo in active RA patients with sDMARD-naïve, inadequately responsive to sDMARDs or TNF-inhibitors...
June 2016: Nihon Rinsho. Japanese Journal of Clinical Medicine
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