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Kinase and rheumatic disease

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https://www.readbyqxmd.com/read/29765992/serological-immunoglobulin-free-light-chain-profile-in-myasthenia-gravis-patients
#1
Umberto Basile, Mariapaola Marino, Cecilia Napodano, Krizia Pocino, Paolo Emilio Alboini, Francesca Gulli, Amelia Evoli, Carlo Provenzano, Emanuela Bartoccioni
Background: Serological levels of free immunoglobulin light chains (FLCs), produced in excess of heavy chains during synthesis of immunoglobulins by plasma cells, can be considered a direct marker of B cell activity in different systemic inflammatory-autoimmune conditions and may represent a useful predictor of rituximab (RTX) therapeutic efficacy, as reported for rheumatoid arthritis and systemic lupus erythematosus. Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction with antibodies (abs) targeting the acetylcholine receptor (AChR) or the muscle-specific tyrosine kinase (MuSK), inducing muscle weakness and excessive fatigability...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29753231/vascular-brain-derived-neurotrophic-factor-pathway-in-rats-with-adjuvant-induced-arthritis-effect-of-anti-rheumatic-drugs
#2
Martin Pedard, Aurore Quirié, Perle Totoson, Frank Verhoeven, Philippe Garnier, Anne Tessier, Céline Demougeot, Christine Marie
BACKGROUND AND AIMS: In rheumatoid arthritis, the control of both disease activity and standard cardiovascular (CV) risk factors is expected to attenuate the increased CV risk. Evidence that brain-derived neurotrophic factor (BDNF) plays a role in vascular biology led us to investigate the vascular BDNF pathway in arthritis rats as well as the interaction between endothelial nitric oxide (NO) and BDNF production. METHODS: The aortic BDNF pathway was studied in rats with adjuvant-induced arthritis, (AIA) using Western blot and immunohistochemical analysis...
May 2, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29731464/-diagnosis-and-treatment-of-rheumatoid-arthritis-toward-the-best-practice-best-practice-with-jak-inhibitors
#3
Kunihiro Yamaoka
Janus kinase(JAK)inhibitor is a new orally available disease modifying anti-rheumatic drug that has shown anti-rheumatic effect resembling biologics. Clinical trials for autoinflammatory and autoimmune diseases are under investigation. Administration route is convenient compared to biologics and possess high anti-rheumatic effect, however specific side effects considered as a class-effect exists. I would like to offer the best conceivable practice with JAK inhibitors based on evidence from clinical trials and real world experiences...
2018: Clinical Calcium
https://www.readbyqxmd.com/read/29671827/molecular-modeling-studies-on-carbazole-carboxamide-based-btk-inhibitors-using-docking-and-structure-based-3d-qsar
#4
Rui Li, Yongli Du, Zhipei Gao, Jingkang Shen
Rheumatoid arthritis (RA) is the second common rheumatic immune disease with chronic, invasive inflammatory characteristics. Non-steroidal anti-inflammatory drugs (NSAIDs), slow-acting anti-rheumatic drugs (SAARDs), or glucocorticoid drugs can improve RA patients’ symptoms, but fail to cure. Broton’s tyrosine kinase (BTK) inhibitors have been proven to be an efficacious target against autoimmune indications and B-cell malignancies. Among the current 11 clinical drugs, only BMS-986142, classified as a carbazole derivative, is used for treating RA...
April 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29669391/translational-biomarkers-and-ex-vivo-models-of-joint-tissues-as-a-tool-for-drug-development-in-rheumatoid-arthritis
#5
Cecilie F Kjelgaard-Petersen, Adam Platt, Martin Braddock, Martin A Jenkins, Kishwar Musa, Emma Graham, Thorbjørn Gantzel, Gillian Slynn, Michael E Weinblatt, Morten A Karsdal, Christian S Thudium, Anne-C Bay-Jensen
OBJECTIVE: Rheumatoid arthritis (RA) is a chronic, autoimmune and degenerative joint disease leading to disability, reduced life quality, and increased mortality. Although several synthetic and biological disease modifying anti-rheumatic drugs (DMARDs) are available, there is still a medical need for novel drugs controlling disease progression. As only 10% of RA drug candidates that enter phase I trials are eventually FDA registered, there is an immediate requirement for translational drug development tools to facilitate early drug development decision making...
April 18, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29663334/the-rheumatic-disease-associated-fam167a-blk-locus-encodes-diora-1-a-novel-disordered-protein-highly-expressed-in-bronchial-epithelium-and-alveolar-macrophages
#6
Lara Mentlein, Gudny Ella Thorlacius, Lauro Meneghel, Lara A Aqrawi, Jorge I Ramírez Sepúlveda, Johan Grunewald, Alexander Espinosa, Marie Wahren-Herlenius
OBJECTIVES: Triggering of autoimmunity that leads to rheumatic disease has been suggested to depend on gene-environment interactions occurring in epithelial barriers and associated immune cells. Genetic studies have identified associations of the FAM167A-BLK locus with rheumatoid arthritis, SLE, and Sjögren's syndrome. While BLK (B lymphocyte kinase) has a well-established role in B cells, family with sequence similarity 167 member A (FAM167A) and its gene family remain uncharacterized...
April 17, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29578342/isolation-characterization-and-structure-activity-relationship-analysis-of-abietane-diterpenoids-from-callicarpa-bodinieri-as-spleen-tyrosine-kinase-inhibitors
#7
Jun-Bo Gao, Shuang-Jing Yang, Zi-Ru Yan, Xing-Jie Zhang, De-Bing Pu, Li-Xia Wang, Xiao-Li Li, Rui-Han Zhang, Wei-Lie Xiao
Species belonging to the genus Callicarpa are used traditionally in Chinese medicine for the treatment of inflammation, rheumatism, and pain. Investigation of the leaves and twigs of Callicarpa bodinieri resulted in the isolation of nine new abietane diterpenoids, bodinieric acids A-I (1-9), along with six known compounds (10-15). The structures of 1-9 were elucidated on the basis of the interpretation of their HRESIMS and NMR data and by ECD calculations. To explore the potential therapeutic target of this plant for immune-mediated disease, the inhibitory activities of the isolates obtained were determined against 13 kinase enzymes...
March 26, 2018: Journal of Natural Products
https://www.readbyqxmd.com/read/29562920/the-safety-of-live-attenuated-vaccines-in-patients-using-il-1-or-il-6-blockade-an-international-survey
#8
Jerold Jeyaratnam, Nienke M Ter Haar, Helen J Lachmann, Ozgur Kasapcopur, Amanda K Ombrello, Donato Rigante, Fatma Dedeoglu, Ezgi H Baris, Sebastiaan J Vastert, Nico M Wulffraat, Joost Frenkel
BACKGROUND: Withholding live-attenuated vaccines in patients using interleukin (IL)-1 or IL-6 blocking agents is recommended by guidelines for both pediatric and adult rheumatic diseases, since there is a risk of infection in an immune suppressed host. However, this has never been studied. This retrospective, multicenter survey aimed to evaluate the safety of live-attenuated vaccines in patients using IL-1 or IL-6 blockade. METHODS: We contacted physicians involved in the treatment of autoinflammatory diseases to investigate potential cases...
March 21, 2018: Pediatric Rheumatology Online Journal
https://www.readbyqxmd.com/read/29545477/therapeutic-effect-of-quinacrine-an-anti-protozoan-drug-by-selective-suppression-of-p-chk1-2-in-p53-negative-malignant-cancers
#9
Soyoung Park, Ah-Young Oh, Jung-Hyun Cho, Min-Ho Yoon, Tae-Guen Woo, Somi Kang, Ho-Young Lee, Yunjin Jung, Bum-Joon Park
Quinacrine (QNC), anti-protozoan drug commonly used against Malaria and Giardiasis, has been recently tried for rheumatics and prion diseases via drug repositioning. In addition, several reports suggest anti-tumor effects of QNC through suppression of NF-κB and activation of p53. This study, demonstrates the anti-cancer effect of QNC via a novel pathway through the elimination of check point kinase 1/2 (Chk1/2) under p53 inactivated conditions. Inhibition of p53, by PFT-α or siRNA, promotes QNC-induced apoptosis in normal fibroblast and p53-intact cancer cells...
March 15, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29512532/-homeostasis-and-disorder-of-musculoskeletal-system-progress-in-the-treatment-of-rheumatoid-arthritis
#10
Yoshiya Tanaka
Rheumatoid arthritis is a systemic autoimmune disease characterized by inflammation and joint damage that causes significant morbidity and mortality. Rapid and appropriate intervention using disease-modifying anti-rheumatic drugs(DMARDs)is prerequisite to halt joint destruction and long-term functional disabilities. Recent progress in the treatment strategy has brought about paradigm shift for the management of the disease, namely, the combined use of methotrexate, a synthetic DMARD, and a biologic DMARD targeting TNF, IL-6 and T cells has revolutionized treatment of rheumatoid arthritis...
2018: Clinical Calcium
https://www.readbyqxmd.com/read/29508003/-pharmacological-treatment-of-rheumatoid-arthritis-and-its-comorbidities
#11
K Krüger
Due to therapeutic advances, rheumatoid arthritis (RA) today has developed into a satisfactorily treatable disease in most cases, with remission being the target of treatment. Early diagnosis with immediate treatment initiation following treat-to-target strategy is the key to a favorable long-term outcome. A guideline-directed treatment algorithm determines the use of conventional synthetic disease-modifying anti-rheumatic drugs (DMARD; e.g., methotrexate), biological DMARD, and targeted oral DMARD (Janus kinase inhibitors)...
April 2018: Der Internist
https://www.readbyqxmd.com/read/29500799/thromboembolism-with-janus-kinase-jak-inhibitors-for-rheumatoid-arthritis-how-real-is-the-risk
#12
Ian C Scott, Samantha L Hider, David L Scott
Two different Janus kinase (JAK) inhibitors-baricitinib and tofacitinib-are effective and licensed in active rheumatoid arthritis (RA). There have been recent concerns about potential thromboembolic risks with these drugs. Concerns about baricitinib focus on clinical trial findings. Using all publically available data, we estimate thromboembolic risks are approximately five events per 1000 patient years with 4 mg baricitinib daily. Concerns about tofacitinib have been raised by analyses of the Federal Drug Administration Adverse Event Reporting System (FAERs)...
March 2, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/29490676/pharmacological-characterisation-of-cr6086-a-potent-prostaglandin-e-2-receptor-4-antagonist-as-a-new-potential-disease-modifying-anti-rheumatic-drug
#13
Gianfranco Caselli, Albino Bonazzi, Marco Lanza, Flora Ferrari, Daniele Maggioni, Cristian Ferioli, Roberto Giambelli, Eleonora Comi, Silvia Zerbi, Marco Perrella, Ornella Letari, Elena Di Luccio, Milena Colovic, Stefano Persiani, Tiziano Zanelli, Laura Mennuni, Tiziana Piepoli, Lucio Claudio Rovati
BACKGROUND: Prostaglandin E2 (PGE2 ) acts via its EP4 receptor as a cytokine amplifier (e.g., interleukin [IL]-6) and induces the differentiation and expansion of inflammatory T-helper (Th) lymphocytes. These mechanisms play a key role in the onset and progression of rheumatoid arthritis (RA). We present the pharmacological characterisation of CR6086, a novel EP4 receptor antagonist, and provide evidence for its potential as a disease-modifying anti-rheumatic drug (DMARD). METHODS: CR6086 affinity and pharmacodynamics were studied in EP4-expressing HEK293 cells by radioligand binding and cyclic adenosine monophosphate (cAMP) production, respectively...
March 1, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29424301/novel-therapeutic-approaches-in-rheumatoid-arthritis-role-of-janus-kinases-inhibitors
#14
Felice Rivellese, Antonio Lobasso, Letizia Barbieri, Bianca Liccardo, Amato De Paulis, Francesca Wanda Rossi
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage and bone destruction and several systemic features. Cardiovascular, pulmonary, psychological, and muscle involvement are the main comorbidities of RA and are responsible for the severity of the disease and long-term prognosis. Pharmacological treatment of rheumatic diseases has evolved remarkably over the past years. In addition, the widespread adoption of treat to target and tight control strategies has led to a substantial improvement of outcomes, so that drug-free remission is nowadays a realistic goal in the treatment of RA...
February 9, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29386201/cd301b-mgl2-mononuclear-phagocytes-orchestrate-autoimmune-cardiac-valve-inflammation-and-fibrosis
#15
Lee A Meier, Jennifer L Auger, Brianna J Engelson, Hannah M Cowan, Elise R Breed, Mayra I Gonzalez-Torres, Joshua D Boyer, Mayank Verma, Aubyn Marath, Bryce A Binstadt
Background -Valvular heart disease (VHD) is common and affects the mitral valve (MV) most frequently. Despite the prevalence of mitral valve disease (MVD), the cellular and molecular pathways that initiate and perpetuate it are not well understood. Methods -K/B.g7 T cell receptor (TCR) transgenic mice spontaneously develop systemic autoantibody-associated autoimmunity, leading to fully-penetrant fibro-inflammatory MVD and arthritis. We used multiparameter flow cytometry, intracellular cytokine staining, and immunofluorescent staining to characterize the cells in inflamed K/B...
January 31, 2018: Circulation
https://www.readbyqxmd.com/read/29314645/tofacitinib-with-conventional-synthetic-disease-modifying-antirheumatic-drugs-in-chinese-patients-with-rheumatoid-arthritis-patient-reported-outcomes-from-a-phase-3-randomized-controlled-trial
#16
Zhanguo Li, Yuan An, Houheng Su, Xiangpei Li, Jianhua Xu, Yi Zheng, Guiye Li, Kenneth Kwok, Lisy Wang, Qizhe Wu
AIM: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We assess the effect of tofacitinib + conventional synthetic disease-modifying anti rheumatic drugs (csDMARDs) on patient-reported outcomes in Chinese patients with RA and inadequate response to DMARDs. METHODS: This analysis of data from the Phase 3 study ORAL Sync included Chinese patients randomized 4 : 4 : 1 : 1 to receive tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, placebo→tofacitinib 5 mg twice daily, or placebo→tofacitinib 10 mg twice daily, with csDMARDs...
February 2018: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/29246242/the-use-of-the-tyrosine-kinase-inhibitor-nilotinib-in-spondyloarthritis-does-targeting-inflammatory-pathways-with-a-treatment-lead-to-vascular-toxicity
#17
REVIEW
Loukman Omarjee, Vincent Jaquinandi, Guillaume Mahe
Spondylarthritis (SpA) is an inflammatory rheumatic disease associated with increased incidence of major adverse cardiovascular events (MACEs). Recently, Paramarta et al. proposed the use of the tyrosine kinase inhibitor Nilotinib in Spondyloarthritis to target certain inflammatory pathways. However, Nilotinib, which is highly effective for the treatment of patients with chronic myeloid leukaemia (CML), is also associated with an increased risk of MACEs. The authors suggest that Nilotinib may be effective in peripheral SpA by modulating inflammation, but not in axial SpA...
December 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29166574/altered-tnf-%C3%AE-response-by-aconibal%C3%A2-and-methotrexate-in-a-lipopolysaccharide-induced-setting-of-inflammatory-conditions-potential-on-a-synergistic-combination
#18
Gunhyuk Park, Seung Hoon Lee, Ji-Ye Han, Dal-Seok Oh
ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii (AC) is a common herbal medicine used as anti-inflammatory and analgesic agent in Eastern Asia. In Korea, a commercial processed AC (Aconibal®) is traditionally used to treat the symptoms of spondylosis deformans and rheumatic pain. AIM OF STUDY: Rheumatoid arthritis (RA) is systemic and autoimmune disease characterized by chronic inflammation. Methotrexate (MTX) is often the first-line therapy for RA. If MTX monotherapy is ineffective or RA is initially severe, adding a tumor necrosis factor alpha (TNF-α) inhibitor to the treatment can be beneficial...
March 1, 2018: Journal of Ethnopharmacology
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
#19
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...
January 2018: 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
#20
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
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