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Interleukin receptor antagonist

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https://www.readbyqxmd.com/read/28107570/efficacy-and-safety-of-interleukin-17-antagonists-in-patients-with-plaque-psoriasis-a-meta-analysis-from-phase-3-randomized-controlled-trails
#1
Dan Wu, Si-Yuan Hou, Shuai Zhao, Lin-Xin Hou, Ting Jiao, Nan-Nan Xu, Ning Zhang
BACKGROUND: The interleukin-17 (IL-17) cytokine pathway plays a key role in the development of psoriasis. Antibodies targeting IL-17 or blocking its receptor may be a new therapeutic approach for psoriasis. To assist treatment selection in daily practice it is essential to understand the benefit and risk profile of IL-17 antagonists. OBJECTIVE: We performed a meta-analysis to evaluate the efficacy and safety of IL-17 antagonists in patients with psoriasis. METHODS: We searched a number of databases for relevant randomized clinical trials (RCTs) published before May 2016...
January 20, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28077582/severity-of-plasma-leakage-is-associated-with-high-levels-of-interferon-%C3%AE-inducible-protein-10-hepatocyte-growth-factor-matrix-metalloproteinase-2-mmp-2-and-mmp-9-during-dengue-virus-infection
#2
Zhisheng Her, Yiu-Wing Kam, Victor C Gan, Bernett Lee, Tun-Linn Thein, Jeslin J L Tan, Linda K Lee, Katja Fink, David C Lye, Laurent Rénia, Yee-Sin Leo, Lisa F P Ng
BACKGROUND:  Dengue virus infection typically causes mild dengue fever, but, in severe cases, life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) occur. The pathophysiological hallmark of DHF and DSS is plasma leakage that leads to enhanced vascular permeability, likely due to a cytokine storm. METHODS:  Ninety patients with dengue during 2010-2012 in Singapore were prospectively recruited and stratified according to their disease phase, primary and secondary infection status, and disease severity, measured by plasma leakage...
January 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28066142/participation-of-central-gabaa-receptors-in-the-trigeminal-processing-of-mechanical-allodynia-in-rats
#3
Min Ji Kim, Young Hong Park, Kui Ye Yang, Jin Sook Ju, Yong Chul Bae, Seong Kyu Han, Dong Kuk Ahn
Here we investigated the central processing mechanisms of mechanical allodynia and found a direct excitatory link with low-threshold input to nociceptive neurons. Experiments were performed on male Sprague-Dawley rats weighing 230-280 g. Subcutaneous injection of interleukin 1 beta (IL-1β) (1 ng/10 µL) was used to produce mechanical allodynia and thermal hyperalgesia. Intracisternal administration of bicuculline, a gamma aminobutyric acid A (GABAA) receptor antagonist, produced mechanical allodynia in the orofacial area under normal conditions...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28063227/lipus-suppressed-lps-induced-il-1%C3%AE-through-the-inhibition-of-nf-%C3%AE%C2%BAb-nuclear-translocation-via-at1-plc%C3%AE-pathway-in-mc3t3-e1
#4
Mayu Nagao, Natsuko Tanabe, Soichiro Manaka, Masako Naito, Kumiko Nakai, Tadahiro Takayama, Takayuki Kawato, Go Torigoe, Jumpei Sekino, Naoya Tsukune, Masao Maeno, Naoto Suzuki, Shuichi Sato
Inflammatory cytokines, interleukin (IL)-1, IL-6, and TNF-a, are involved in inflammatory bone diseases such as rheumatoid osteoarthritis and periodontal disease. Particularly, periodontal disease, which destroys alveolar bone, is stimulated by lipopolysaccharide (LPS). Low-intensity pulsed ultrasound (LIPUS) is used for bone healing in orthopedics and dental treatments. However,the mechanism underlying effects of LIPUS on LPS-induced inflammatory cytokine are not well understood. We therefore aimed to investigate the role of LIPUS on LPS-induced IL-1a production...
January 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28060893/positioning-of-tacrolimus-for-the-treatment-of-diabetic-nephropathy-based-on-computational-network-analysis
#5
Constantin Aschauer, Paul Perco, Andreas Heinzel, Judith Sunzenauer, Rainer Oberbauer
OBJECTIVE: To evaluate tacrolimus as therapeutic option for diabetic nephropathy (DN) based on molecular profile and network-based molecular model comparisons. MATERIALS AND METHODS: We generated molecular models representing pathophysiological mechanisms of DN and tacrolimus mechanism of action (MoA) based on literature derived data and transcriptomics datasets. Shared enriched molecular pathways were identified based on both model datasets. A newly generated transcriptomics dataset studying the effect of tacrolimus on mesangial cells in vitro was added to identify mechanisms in DN pathophysiology...
2017: PloS One
https://www.readbyqxmd.com/read/28032234/the-emerging-role-of-interleukin-il-1-in-the-pathogenesis-and-treatment-of-inflammatory-and-degenerative-eye-diseases
#6
Claudia Fabiani, Jurgen Sota, Gian Marco Tosi, Rossella Franceschini, Bruno Frediani, Mauro Galeazzi, Donato Rigante, Luca Cantarini
Interleukin (IL)-1 plays a key role in the pathogenesis and thereafter in the search for specific treatments of different inflammatory and degenerative eye diseases. Indeed, an overactivity of IL-1 might be an initiating factor for many immunopathologic sceneries in the eye, as proven by the efficacy of the specific IL-1 blockade in different ocular diseases. For instance, the uveitis in monogenic autoinflammatory disorders, such as Blau syndrome and cryopyrin-associated periodic syndrome, or in complex polygenic autoinflammatory disorders, such as Behçet's disease, has been successfully treated with IL-1 blockers...
December 28, 2016: Clinical Rheumatology
https://www.readbyqxmd.com/read/28030558/loss-of-trpv4-function-suppresses-inflammatory-fibrosis-induced-by-alkali-burning-mouse-corneas
#7
Yuka Okada, Kumi Shirai, Masayasu Miyajima, Peter S Reinach, Osamu Yamanaka, Takayoshi Sumioka, Masahide Kokado, Katsuo Tomoyose, Shizuya Saika
In humans suffering from pulmonary disease and a mouse model, transient receptor potential vanilloid 4 (TRPV4) channel activation contributes to fibrosis. As a corneal alkali burn induces the same response, we determined if such an effect is also attributable to TRPV4 activation in mice. Accordingly, we determined if the alkali burn wound healing responses in wild-type (WT) mice are different than those in their TRPV4-null (KO) counterpart. Stromal opacification due to fibrosis in KO (n = 128) mice was markedly reduced after 20 days relative to that in WT (n = 157) mice...
2016: PloS One
https://www.readbyqxmd.com/read/28028363/c5a-c5ar-pathway-is-essential-for-up-regulating-sphk1-expression-through-p38-mapk-activation-in-acute-liver-failure
#8
Yan-Chang Lei, Chun-Lei Lu, Ling Chen, Ke Ge, Ling-Ling Yang, Wen Li, Yuan-Hua Wu
AIM: To investigate the role of the complement 5a (C5a)/C5a receptor (C5aR) pathway in the pathogenesis of acute liver failure (ALF) in a mouse model. METHODS: BALB/c mice were randomly assigned to different groups, and intraperitoneal injections of lipopolysaccharide (LPS)/D-galactosamine (D-GalN) (600 mg/kg and 10 μg/kg) were used to induce ALF. The Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase (ALT) levels, at different time points within a 1-wk period, were detected with a biochemistry analyzer...
December 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28027695/inhibitory-mechanism-of-the-outer-membrane-growth-of-chronic-subdural-hematomas
#9
Koji Osuka, Yasuo Watanabe, Nobuteru Usuda, Masahiro Aoyama, Kenichiro Iwami, Mikinobu Takeuchi, Takeya Watabe, Masakazu Takayasu
We previously demonstrated that the inflammatory cytokine interleukin-6 (IL-6) activates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway in fibroblasts within the outer membranes of chronic subdural hematomas (CSDHs), and the activation of this pathway may induce CSDH outer membrane growth. The inhibitory system for this signal transduction pathway is unknown. CSDH fluids were obtained from ten patients during trepanation surgery as the case group, and CSF samples were obtained from seven patients suffering from subarachnoid hemorrhage (SAH) on day 1 as the control group...
December 27, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28025040/acetylcholine-released-from-t-cells-regulates-intracellular-ca-2-il-2-secretion-and-t-cell-proliferation-through-nicotinic-acetylcholine-receptor
#10
Masato Mashimo, Yukari Iwasaki, Shoko Inoue, Shoko Saito, Koichiro Kawashima, Takeshi Fujii
AIMS: T lymphocytes synthesize acetylcholine (ACh) and express muscarinic and nicotinic ACh receptors (mAChR and nAChR, respectively) responsible for increases in the intracellular Ca(2+) concentration ([Ca(2+)]i). Our aim in the present study was to assess whether autocrine ACh released from T lymphocytes regulates their physiological functions. MAIN METHODS: MOLT-3 human leukemic cell line and murine splenocytes were loaded with fura-2 to monitor [Ca(2+)]i changes in the absence or presence of several AChR antagonists, including mecamylamine, methyllycaconitine and scopolamine...
December 23, 2016: Life Sciences
https://www.readbyqxmd.com/read/28018220/the-angiotensin-1-7-mas-axis-counteracts-angiotensin-ii-dependent-and-independent-pro-inflammatory-signaling-in-human-vascular-smooth-muscle-cells
#11
Laura A Villalobos, Álvaro San Hipólito-Luengo, Mariella Ramos-González, Elena Cercas, Susana Vallejo, Alejandra Romero, Tania Romacho, Raffaele Carraro, Carlos F Sánchez-Ferrer, Concepción Peiró
Background and Aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7) is a member of the renin-angiotensin system (RAS) that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7) to counteract human aortic smooth muscle cell (HASMC) inflammation triggered by RAS-dependent and -independent stimuli, such as Ang II or interleukin (IL)-1β...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28012280/whey-and-casein-proteins-and-medium-chain-saturated-fatty-acids-from-milk-do-not-increase-low-grade-inflammation-in-abdominally-obese-adults
#12
Mette Bohl, Ann Bjørnshave, Søren Gregersen, Kjeld Hermansen
BACKGROUND: Low-grade inflammation is involved in the development of diabetes and cardiovascular disease (CVD). Inflammation can be modulated by dietary factors. Dairy products are rich in saturated fatty acids (SFA), which are known to possess pro-inflammatory properties. However, different fatty acid compositions may exert different effects. Other components such as milk proteins may exert anti-inflammatory properties which may compensate for the potential negative effects of SFAs. Generally, the available data suggest a neutral role of dairy product consumption on inflammation...
July 2016: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28011791/maternal-smoking-and-newborn-cytokine-and-immunoglobulin-levels
#13
Nikhita Chahal, Alexander C McLain, Akhgar Ghassabian, Kara A Michels, Erin M Bell, David A Lawrence, Edwina H Yeung
INTRODUCTION: Prenatal smoking exposure may lead to permanent changes in neonatal inflammation and immune response that have lifelong implications, including increased risks for atopy and respiratory disorders. METHODS: The effect of maternal smoking on neonatal biomarkers of inflammation and immune response was assessed among 3459 singletons and twins in the Upstate KIDS Study. The following inflammatory biomarkers were measured using newborn dried blood spots (DBSs): interleukin (IL)-1α, IL-1 receptor antagonist, IL-6, IL-8, C-reactive protein, and tumor necrosis factor alpha...
December 23, 2016: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
https://www.readbyqxmd.com/read/28009628/enhanced-delivery-of-il-1-receptor-antagonist-to-the-cns-as-a-novel-anti-tfr-il-1ra-fusion-reverses-neuropathic-mechanical-hypersensitivity
#14
Carl I Webster, Jon Hatcher, Matthew Burrell, George Thom, Peter Thornton, Ian Gurrell, Iain Chessell
Neuropathic pain is a major unmet medical need, with only 30-35 % of patients responding to the current standard of care. The discovery and development of novel therapeutics to address this unmet need have been hampered by poor target engagement, the selectivity of novel molecules, and limited access to the relevant compartments. Biologic therapeutics, either monoclonal antibodies (mAb) or peptides, offer a solution to the challenge of specificity as the intrinsic selectivity of these kinds of molecules is significantly higher than traditional medicinal chemistry-derived approaches...
December 20, 2016: Pain
https://www.readbyqxmd.com/read/28007559/macrophage-mediated-clofazimine-sequestration-is-accompanied-by-a-shift-in-host-energy-metabolism
#15
Julie Trexel, Gi S Yoon, Rahul K Keswani, Cora McHugh, Larisa Yeomans, Victor Vitvitsky, Ruma Banerjee, Sudha Sud, Yihan Sun, Gus R Rosania, Kathleen A Stringer
Prolonged (8 weeks) oral administration of clofazimine results in a profound pharmacodynamic response- bioaccumulation in macrophages (including Kupffer cells) as intracellular crystal-like drug inclusions (CLDIs) with an associated increase in interleukin-1 receptor antagonist production. Notably, CLDI formation in Kupffer cells concomitantly occurs with the formation of macrophage-centric granulomas. Accordingly, we sought to understand the impact of these events on host metabolism using (1)H-nuclear magnetic resonance metabolomics...
December 19, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27995367/paracoccidioides-brasiliensis-induces-cytokine-secretion-in-epithelial-cells-in-a-protease-activated-receptor-dependent-par-manner
#16
Priscila de Oliveira, Maria Aparecida Juliano, Aparecida Sadae Tanaka, Adriana Karaoglanovic Carmona, Saara Maria Batista Dos Santos, Bianca Carla Silva Campitelli de Barros, Paloma Korehisa Maza, Rosana Puccia, Erika Suzuki
Paracoccidioides brasiliensis is one of the etiological agents of the human systemic mycosis paracoccidioidomycosis. Protease-activated receptors (PARs) are expressed in many cell types and comprise a family of G protein-coupled receptors (PAR-1, PAR-2, and PAR-4), which may be activated by proteases secreted by several pathogens. In the present study, we showed that the pathogenic fungus P. brasiliensis secretes components that promote interleukin (IL)-6 and IL-8 secretion by the lung epithelial cell line A549...
December 19, 2016: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/27993689/constriction-of-the-buccal-branch-of-the-facial-nerve-produces-unilateral-craniofacial-allodynia
#17
Susannah S Lewis, Peter M Grace, Mark R Hutchinson, Steven F Maier, Linda R Watkins
Despite pain being a sensory experience, studies of spinal cord ventral root damage have demonstrated that motor neuron injury can induce neuropathic pain. Whether injury of cranial motor nerves can also produce nociceptive hypersensitivity has not been addressed. Herein, we demonstrate that chronic constriction injury (CCI) of the buccal branch of the facial nerve results in long-lasting, unilateral allodynia in the rat. An anterograde and retrograde tracer (3000MW tetramethylrhodamine-conjugated dextran) was not transported to the trigeminal ganglion when applied to the injury site, but was transported to the facial nucleus, indicating that this nerve branch is not composed of trigeminal sensory neurons...
December 18, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27991924/cooperation-among-heterogeneous-prostate-cancer-cells-in-the-bone-metastatic-niche
#18
K Shahriari, F Shen, A Worrede-Mahdi, Q Liu, Y Gong, F U Garcia, A Fatatis
The growth of disseminated tumor cells into metastatic lesions depends on the establishment of a favorable microenvironment in the stroma of the target organs. Here we show that mice treated with anakinra, an antagonist of the interleukin (IL)-1β receptor (IL-1R), or harboring a targeted deletion of IL-1R are significantly less prone to develop bone tumors when inoculated in the arterial circulation with human prostate cancer (PCa) cells expressing IL-1β. Interestingly, human mesenchymal stem cells exposed in vitro to medium conditioned by IL-1β-expressing cancer cells responded by upregulating S100A4, a marker of cancer-associated fibroblasts (CAFs), and this effect was blocked by anakinra...
December 19, 2016: Oncogene
https://www.readbyqxmd.com/read/27986325/effects-of-transient-receptor-potential-canonical-1-trpc1-on-the-mechanical-stretch-induced-expression-of-airway-remodeling-associated-factors-in-human-bronchial-epithelioid-cells
#19
Qian Yu, Minchao Li
Research has shown that mechanical stress stimulation can cause airway remodeling. We investigate the effects of mechanical stretch on the expression of the airway remodeling-associated factors interleukin-13 (IL-13) and matrix metalloprotein-9 (MMP-9) and signaling pathways in human bronchial epithelioid (16HBE) cells under mechanical stretch. A Flexcell FX-4000 Tension System with a flexible substrate was applied to stretch 16HBE cells at a 15% elongation amplitude and 1Hz frequency, with stretching for 0...
January 25, 2017: Journal of Biomechanics
https://www.readbyqxmd.com/read/27983945/the-effect-of-memantine-on-trinitrobenzene-sulfonic-acid-induced-ulcerative-colitis-in-mice
#20
Ehsan Motaghi, Valiollah Hajhashemi, Parvin Mahzouni, Mohsen Minaiyan
Previous reports suggest a significant role for N-Methyl-D-aspartate (NMDA) activation in inflammatory processes. So, this study was conducted to investigate the effect of memantine, a commonly used NMDA receptor antagonist, on inflammatory changes in mice model of colitis. Colitis was induced by intracolonic instillation of trinitrobenzene sulfonic acid (TNBS) (40mg/kg). Animals received memantine (12.5, 25 and 50mg/kg, i.p.), glutamate (2g/kg, p.o.) or dexamethasone (1mg/kg, i.p.) 24h before TNBS instillation and daily thereafter for 4 days...
October 27, 2016: European Journal of Pharmacology
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