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https://www.readbyqxmd.com/read/28820959/takinib-a-selective-tak1-inhibitor-broadens-the-therapeutic-efficacy-of-tnf-%C3%AE-inhibition-for-cancer-and-autoimmune-disease
#1
Juliane Totzke, Deepak Gurbani, Rene Raphemot, Philip F Hughes, Khaldon Bodoor, David A Carlson, David R Loiselle, Asim K Bera, Liesl S Eibschutz, Marisha M Perkins, Amber L Eubanks, Phillip L Campbell, David A Fox, Kenneth D Westover, Timothy A J Haystead, Emily R Derbyshire
Tumor necrosis factor alpha (TNF-α) has both positive and negative roles in human disease. In certain cancers, TNF-α is infused locally to promote tumor regression, but dose-limiting inflammatory effects limit broader utility. In autoimmune disease, anti-TNF-α antibodies control inflammation in most patients, but these benefits are offset during chronic treatment. TAK1 acts as a key mediator between survival and cell death in TNF-α-mediated signaling. Here, we describe Takinib, a potent and selective TAK1 inhibitor that induces apoptosis following TNF-α stimulation in cell models of rheumatoid arthritis and metastatic breast cancer...
August 17, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28820392/orally-administered-angiotensin-converting-enzyme-inhibitors-captopril-and-isoleucine-proline-proline-have-distinct-effects-on-local-renin-angiotensin-system-and-corticosterone-synthesis-in-dextran-sulfate-sodium-induced-colitis-in-mice
#2
H Salmenkari, M Holappa, R A Forsgard, R Korpela, H Vapaatalo
The effects of angiotensin-converting enzyme (ACE) inhibition by an antihypertensive drug, captopril, and milk casein-derived ACE-inhibiting bioactive tripeptide isoleucine-proline-proline (Ile-Pro-Pro), on local renin-angiotensin system (RAS) and glucocorticoid production in the intestine were studied in the dextran sodium sulfate induced colitis in mice. Mice received water or 3% dextran sodium sulfate with or without either 15.7 mg/l captopril or 833 mg/l Ile-Pro-Pro for 7 days. Captopril and Ile-Pro-Pro were found to have distinct effects on local renin-angiotensin system and mRNA expression of glucocorticoid synthesis components in colon in vitro...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28819716/neurological-complications-of-therapeutic-monoclonal-antibodies-trends-from-oncology-to-rheumatology
#3
REVIEW
Chandler Gill, Stasia Rouse, Ryan D Jacobson
PURPOSE OF REVIEW: This review is to describe the scope of neurological complications associated with monoclonal antibody-based therapies, applied across medical specialties, to demonstrate the common and rare neurological syndromes that may be encountered in clinical practice according to the therapeutic agent being receive, and to explain appropriate work-up, diagnosis, and management of drug complications, as supported by the literature. RECENT FINDINGS: The number of commercially available, evidence-based therapeutic monoclonal antibodies continues to expand...
August 17, 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28815968/discovery-of-naphthyl-n-acylhydrazone-p38%C3%AE-mapk-inhibitors-with-in-vivo-anti-inflammatory-and-anti-tnf-%C3%AE-activity
#4
Rosana H C N Freitas, Natália M Cordeiro, Patrícia R Carvalho, Marina A Alves, Isabella A Guedes, Tayna S Valerio, Laurent E Dardenne, Lídia M Lima, Eliezer J Barreiro, Patrícia D Fernandes, Carlos A M Fraga
Protein kinases constitute attractive therapeutic targets for development of new prototypes to treat different chronic diseases. Several available drugs, like tinibs, are tyrosine kinase inhibitors, meanwhile, inhibitors of serine/threonine kinases, such as mitogen-activated protein kinase (MAPK) are still trying to overcome some problems in one of the steps of clinical development to become drugs. So, here we reported the synthesis, the in vitro kinase inhibitory profile, docking studies and the evaluation of anti-inflammatory profile of new naphthyl-N-acylhydrazone derivatives using animal models...
August 17, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28814890/clinical-and-economic-analysis-of-outcomes-of-dose-tapering-or-withdrawal-of-tumor-necrosis-factor-%C3%AE-inhibitors-upon-achieving-stable-disease-activity-in-rheumatoid-arthritis-patients
#5
Daniel Aletaha, Sonya J Snedecor, Varun Ektare, Mei Xue, Yanjun Bao, Vishvas Garg
OBJECTIVE: To compare the real-world, 5-year clinical and cost impact of maintaining treatment with the tumor necrosis factor-α inhibitors (anti-TNFs) adalimumab, etanercept, or infliximab vs dose tapering or withdrawal in rheumatoid arthritis (RA) patients who have achieved remission (defined as a 28-joint count Disease Activity Score [DAS28] < 2.6) or low disease activity (LDA; DAS28 < 3.2). METHODS: Using a 5-year Markov model with 1-month cycle length, we examined the clinical and cost impact of three treatment strategies: withdrawal, tapering, or maintenance of anti-TNFs among RA patients in remission or who have achieved LDA...
2017: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/28814312/rationale-and-design-of-the-brigham-cohort-for-psoriasis-and-psoriatic-arthritis-registry-coppar
#6
Maria Schneeweiss, Joseph F Merola, Elizabeth W Karlson, Daniel H Solomon
BACKGROUND: Psoriasis (PsO) and psoriatic arthritis (PsA) are related conditions with poorly defined transition among them, risk factors for progression, complex treatment algorithms, and biomarkers for treatment response and long-term outcomes. We describe the development of a PsO/PsA registry at an academic medical center. METHODS: We developed a single-center PsO/PsA longitudinal disease registry including biorepository that captures relevant disease markers and treatment choices in a circumscribed population with a defined catchment area...
August 16, 2017: BMC Dermatology
https://www.readbyqxmd.com/read/28812210/increased-il-6-expression-on-thp-1-by-il-34-stimulation-up-regulated-rheumatoid-arthritis-th17-cells
#7
Bing Wang, Yawei Tang, Xiaotong Sun, Xunli Ouyang, Han Li, Jing Wei, Yan Zhang, Xia Li
IL-34 is a pleiotropic cytokine, which is a key regulator of monocytes/macrophages and might participate in the pathogenesis of RA. In this study, we aimed to explore the effect of IL-34 on the monocyte-like cell line THP-1 and the quantitative variation of Th17 cells in THP-1 and RA CD4(+)T cells coculture system. CD4(+)T cells were purified from RA PBMC using immunomagnetic beads. THP-1 were cultured with RA CD4(+)T cells. The frequency of Th17 cells was determined by FACS. Fluorscence indensity and expression of ROS were detected by FACS and cell staining, respectively...
August 15, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28812149/-uveitis-in-spondyloarthritis
#8
REVIEW
M Rudwaleit, K Walscheid, A Heiligenhaus
Acute anterior uveitis (AAU) is the most frequent uveitis subtype. It is often associated with HLA-B27 and with inflammatory rheumatic diseases, in particular with spondyloarthritis (SpA), which itself is strongly associated with HLA-B27. About 40-60% of patients with AAU have an associated spondyloarthritis, and 20-40% of patients with spondyloarthritis also have uveitis. The incidence of AAU in patients with SpA clearly correlates with disease duration. The AAU has an acute onset, usually affects only one eye at a time, and shows a tendency for recurrence...
August 15, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28811745/inhibition-of-inflammation-mediated-through-the-tumor-necrosis-factor-%C3%AE-biochemical-pathway-can-lead-to-favorable-outcomes-in-alzheimer-disease
#9
REVIEW
Daniah Shamim, Michael Laskowski
Tumor necrosis factor α (TNF-α) inhibitors have long been used as disease-modifying agents in immune disorders. Recently, research has shown a role of chronic neuroinflammation in the pathophysiology of neurodegenerative diseases such as Alzheimer disease, and interest has been generated in the use of anti-TNF agents and TNF-modulating agents for prevention and treatment. This article extensively reviewed literature on animal studies testing these agents. The results showed a role for direct and indirect TNF-α inhibition through agents such as thalidomide, 3,6-dithiothalidomide, etanercept, infliximab, exendin-4, sodium hydrosulfide, minocycline, imipramine, and atorvastatin...
2017: Journal of Central Nervous System Disease
https://www.readbyqxmd.com/read/28811547/up-regulation-of-nadph-oxidase-mediated-redox-signaling-contributes-to-the-loss-of-barrier-function-in-krit1-deficient-endothelium
#10
Luca Goitre, Peter V DiStefano, Andrea Moglia, Nicholas Nobiletti, Eva Baldini, Lorenza Trabalzini, Julie Keubel, Eliana Trapani, Vladimir V Shuvaev, Vladimir R Muzykantov, Ingrid H Sarelius, Saverio Francesco Retta, Angela J Glading
The intracellular scaffold KRIT1/CCM1 is an established regulator of vascular barrier function. Loss of KRIT1 leads to decreased microvessel barrier function and to the development of the vascular disorder Cerebral Cavernous Malformation (CCM). However, how loss of KRIT1 causes the subsequent deficit in barrier function remains undefined. Previous studies have shown that loss of KRIT1 increases the production of reactive oxygen species (ROS) and exacerbates vascular permeability triggered by several inflammatory stimuli, but not TNF-α...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810537/cilostazol-protects-mice-against-myocardium-ischemic-reperfusion-injury-by-activating-a-ppar%C3%AE-jak2-stat3-pathway
#11
Jiangjin Li, Xiaoli Xiang, Xiaoxuan Gong, Yafei Shi, Jing Yang, Zuo Xu
Myocardial ischemia/reperfusion (MIR) injury causes severe arrhythmias and a high lethality. The present study is designed to investigate the effect of cilostazol on MIR injury and the underlying mechaism. We measured the effects of cilostazol on heart function parameters in a mouse model of MIR. Proinflammatory cytokines and apoptosis proteins in the myocardium were examined to investigate the anti-inflammatory and anti-apoptosis ability of cilostazol. The participation of PPARγ/JAK2/STAT3 pathway was investigated...
August 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28808378/rutamarin-an-active-constituent-from-ruta-angustifolia-pers-induced-apoptotic-cell-death-in-the-ht29-colon-adenocarcinoma-cell-line
#12
Shafinah Ahmad Suhaimi, Sok Lai Hong, Sri Nurestri Abdul Malek
BACKGROUND: Ruta angustifolia Pers. is a perennial herb that is cultivated worldwide, including Southeast Asia, for the treatment of various diseases as traditional medicine. OBJECTIVE: The purpose of the study was to identify an active principle of R. angustifolia and to investigate its effect on the HT29 cell death. MATERIALS AND METHODS: The methanol and fractionated extracts (hexane, chloroform, ethyl acetate, and water) of R. angustifolia Pers...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28808187/g-aminobutyric-acid-promotes-methionine-choline-deficient-diet-induced-nonalcoholic-steatohepatitis
#13
Yoon Seok Roh, Ara Cho, Zixiong Zhou, Hyuneui Jeong, Jeong-Eun Park, Youn-Soo Cha, Suk-Heung Oh, Chae-Woong Lim, Bumseok Kim
Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and a major cause of liver fibrosis worldwide. G-Aminobutyric acid (GABA) is one of the most abundant inhibitory neurotransmitters in the central nervous system. Recently, it has been reported that GABAergic signaling pathways are found in various non-neuronal tissues including the immune system and play a functional role. In the present study, we investigated whether administration of GABA has effects on NASH through its immunomodulatory effects...
October 17, 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28807222/polymyxin-b-as-an-inhibitor-of-lipopolysaccharides-contamination-of-herb-crude-polysaccharides-in-mononuclear-cells
#14
Xiao-Xiao Lu, Yi-Fan Jiang, Hong Li, Ying-Ye Ou, Zhi-De Zhang, Hong-Ye DI, Dao-Feng Chen, Yun-Yi Zhang
Lipopolysaccharides (LPS) contamination in herbal crude polysaccharides is inevitable. The present study was performed to explore the effect of polymyxin B on abolishing the influence of LPS contamination in mononuclear cells. LPS was pretreated with polymyxin B sulfate (PB) at different concentrations for 1, 5 or 24 h, and then used to stimulate RAW264.7 and mouse peritoneal macrophages (MPMs). The nitric oxide (NO) and tumor necrosis factor-α (TNF-α) in cell culture supernatant, as the indications of cell response, were assayed...
July 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28806729/erk2-and-jnk1-contribute-to-tnf-%C3%AE-induced-il-8-expression-in-synovial-fibroblasts
#15
Shinichi Namba, Rei Nakano, Taku Kitanaka, Nanako Kitanaka, Tomohiro Nakayama, Hiroshi Sugiya
Tumor necrosis factor α (TNF-α) induces the expression and secretion of interleukin 8 (IL-8), which contributes to synovitis in rheumatoid arthritis (RA). To elucidate the mechanism of the onset of RA, we used synovial fibroblasts without autoimmune inflammatory diseases and investigated MAPK signaling pathways in TNF-α-induced IL-8 expression. Synovial fibroblasts isolated from healthy dogs were characterized by flow cytometry, which were positive for the fibroblast markers CD29, CD44, and CD90 but negative for the hematopoietic cell markers CD14, CD34, CD45, and HLA-DR...
2017: PloS One
https://www.readbyqxmd.com/read/28804940/effects-of-polymyxin-b-on-tnf-%C3%AE-production-in-equine-whole-blood-stimulated-with-three-different-bacterial-toxins
#16
J R Bauquier, B S Tennent-Brown, E Tudor, S R Bailey
Polymyxin-B is used to treat equine systemic inflammation. Bacterial toxins other than lipopolysaccharide (LPS) contribute to systemic inflammation but the effects of polymyxin-B on these are poorly defined. Whole blood aliquots from six healthy horses diluted 1:1 with RPMI were incubated for 21 hr with 1 μg/ml of LPS, lipoteichoic acid (LTA) or peptidoglycan (PGN) in the presence of increasing concentrations of polymyxin-B (10-3000 μg/ml). A murine L929 fibroblast bioassay was used to measure TNF-α activity...
August 14, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28804558/nadph-oxidase-2-inhibitor-diphenyleneiodonium-enhances-ros-independent-bacterial-phagocytosis-in-murine-macrophages-via-activation-of-the-calcium-mediated-p38-mapk-signaling-pathway
#17
Yuanfeng Zhu, Shijun Fan, Ning Wang, Xiaoli Chen, Yongjun Yang, Yongling Lu, Qian Chen, Jiang Zheng, Xin Liu
Activation of NADPH oxidase 2 (NOX2) triggers reactive oxygen species (ROS) generation, both of which are essential for robust microbial clearance by phagocytes. However, it is unknown whether inhibition of NOX2 activation or ROS generation affects cellular phagocytosis. Here, we found that the classic NOX2 inhibitor diphenyleneiodonium (DPI) induced uptake of E. coli by murine peritoneal macrophages through enhancing phagocytosis, and this effect was temperature-sensitive and attenuated by cytochalasin D as well as chemical inhibition of Syk and PLCγ, two downstream kinases involved in actin polymerization during phagocytosis...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28803066/a-novel-ripk1-inhibitor-that-prevents-retinal-degeneration-in-a-rat-glaucoma-model
#18
Yun-Ju Do, Jee-Won Sul, Ki-Hong Jang, Nam Sook Kang, Young-Hoon Kim, Young-Gwan Kim, Eunhee Kim
In glaucoma, retinal ganglion cells (RGCs) are exposed to ischemic stress with elevation of the intraocular pressure and are subsequently lost. Necroptosis, a type of regulated necrosis, is known to play a pivotal role in this loss. We observed that receptor-interacting protein kinase 1 (RIPK1), the key player of necroptosis, was activated by diverse ischemic stresses, including TCZ, chemical hypoxia (CH), and oxygen glucose deprivation (OGD). In this study, we introduce a RIPK1-inhibitory compound (RIC) with a novel scaffold...
August 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28800780/a-novel-scoring-system-based-on-common-laboratory-tests-predicts-the-efficacy-of-tnf-inhibitor-and-il-6-targeted-therapy-in-patients-with-rheumatoid-arthritis-a-retrospective-multicenter-observational-study
#19
Jin Nakagawa, Yoshinobu Koyama, Atsushi Kawakami, Yukitaka Ueki, Hiroshi Tsukamoto, Takahiko Horiuchi, Shuji Nagano, Ayumi Uchino, Toshiyuki Ota, Mitsuteru Akahoshi, Koichi Akashi
BACKGROUND: Currently, although several categories of biological disease-modifying antirheumatic drugs (bDMARDs) are available, there are few data informing selection of initial treatment for individual patients with rheumatoid arthritis (RA). Therefore, tumor necrosis factor inhibitor (TNF-i) and tocilizumab (TCZ) are treated as equivalent treatments in the recent disease management recommendations. We focused on two anticytokine therapies, TCZ and TNF-i, and aimed to develop a scoring system that predicts a better treatment for each RA patient before starting an IL-6 or a TNF-i...
August 11, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28800777/bortezomib-treatment-induces-a-higher-mortality-rate-in-lupus-model-mice-with-a-higher-disease-activity
#20
Tomoko Ikeda, Hiroshi Fujii, Masato Nose, Yukiko Kamogawa, Tsuyoshi Shirai, Yuko Shirota, Tomonori Ishii, Hideo Harigae
BACKGROUND: Bortezomib (Bz) is a proteasome inhibitor that directly targets antibody-producing plasma cells. We recently reported the first randomized control trial that evaluated the effects of Bz in patients with systemic lupus erythematosus (SLE). In that study, we demonstrated that Bz treatment is associated with many adverse reactions in patients with refractory disease. In the present study, we examine the therapeutic and toxic effects of Bz on MRL/MpJ-lpr/lpr (MRL/lpr) mice with severe disease activity...
August 11, 2017: Arthritis Research & Therapy
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