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https://www.readbyqxmd.com/read/28431280/interleukin-1-receptor-associated-kinase-1-is-a-potential-therapeutic-target-of-anti-inflammatory-therapy-for-systemic-lupus-erythematosus
#1
Mingfang Li, Datang Yu, Bing Ni, Fei Hao
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease and currently has no effective therapy. The genome-wide analyses indicate that interleukin-1 receptor associated kinase 1 (IRAK1) is associated with the susceptibility of SLE in humans. In the present study, we identified that IRAK1 was overexpressed and hyper-activated in splenic mononuclear cells from B6.MRL-Fas(lpr)/Nju (B6.lpr) mice and peripheral blood mononuclear cells (PBMCs) from SLE patients. Intraperitoneal treatment with a small molecular inhibitor of IRAK1 (IRAK1/4 inhibitor or IRAK-Inh) significantly mitigated inflammatory responses and renal injury in B6...
April 18, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28430696/sequential-analysis-of-a-panel-of-biomarkers-and-pathologic-findings-in-a-resuscitated-rat-model-of-sepsis-and-recovery
#2
Nishkantha Arulkumaran, Marije L Sixma, Elisa Jentho, Elias Ceravola, Paul S Bass, John A Kellum, Robert J Unwin, Fred W K Tam, Mervyn Singer
OBJECTIVES: To characterize the temporal pattern of a panel of blood and urinary biomarkers in an animal model of fecal peritonitis and recovery. DESIGN: Prospective observational animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: A fluid-resuscitated, long-term (3 d) rat model of sepsis (fecal peritonitis) and recovery was used to understand the temporal association of sepsis biomarkers in relation to systemic hemodynamics, inflammation, and renal function...
April 20, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28430601/growth-suppressive-activity-of-raloxifene-on-liver-cancer-cells-by-targeting-il-6-gp130-signaling
#3
Yina Wang, Haiyan Ma, Chongqiang Zhao, Tianshu Liu, Dan Yan, David Jou, Huameng Li, Cuntai Zhang, Jiagao Lü, Chenglong Li, Jiayuh Lin, Sheng Li, Li Lin
BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine, which is involved in the regulation of differentiation and growth of certain types of tumor cells. Constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) induced by IL-6 is frequently detected in liver cancer and has emerged as a viable molecular target for liver cancer treatment. However, few inhibitors targeting up-streams of STAT3 are available for the therapy of liver cancer. We reported the discovery of EVISTA (Raloxifene HCl) as novel inhibitor of IL-6/GP130 protein-protein interactions (PPIs) using multiple ligand simultaneous docking (MLSD) and drug repositioning...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429995/new-insights-into-the-role-of-dietary-spermine-on-inflammation-immune-function-and-related-signalling-molecules-in-the-thymus-and-spleen-of-piglets
#4
Wei Cao, Xianjian Wu, Gang Jia, Hua Zhao, Xiaoling Chen, Caimei Wu, Jiayong Tang, Jing Wang, Jingyi Cai, Guangmang Liu
This study aimed to determine the effects of dietary spermine supplementation on the inflammatory response and immune function of the thymus and spleen in piglets. Eighty suckling piglets were randomly assigned to receive adequate nutrients supplemented with spermine (0.4 mmol/kg body weight) or restricted nutrient intake supplemented with normal saline for 7 h or 3, 6 and 9 days in pairs. Regardless of treatment time, spermine supplementation decreased (p < 0.05, compared with the controls) the following: (1) tumour necrosis factor α (TNF-α), interleukin (IL)-1β, 2 and 6, and interferon (IFN)-γ levels in serum; (2) gene expression of cluster of differentiation 8 and integrin beta-2 in the thymus and spleen and the lymphocyte function-associated antigen 1 in the thymus; (3) mRNA levels of TNF-α, IL 1β, 2, 6, and 12, IFN-γ and inducible nitric oxide synthase in the thymus and spleen, as well as IL-8 in the spleen; and (4) eukaryotic IF4E-binding protein 1, Janus kinase 2, signal transducer and activator of transcription 3, and nuclear factor-kappa B P65 gene transcriptions in the thymus and spleen...
June 2017: Archives of Animal Nutrition
https://www.readbyqxmd.com/read/28429935/saponins-ginsenosides-from-the-leaves-of-panax-quinquefolius-ameliorated-acetaminophen-induced-hepatotoxicity-in-mice
#5
Xingyue Xu, Junnan Hu, Zhi Liu, Rui Zhang, Yufang He, Wei Hou, Zhiqing Wang, Ge Yang, Wei Li
Acetaminophen (APAP) overdose is the most frequent inducement of drug-induced acute liver injury (ALI). The purpose of this study was to investigate the protective effect of saponins (ginsenosides) from the leaves of Panax quinquefolius (PQS) against APAP-induced hepatotoxicity and the involved mechanism were investigated. Mice were pretreated with PQS (150 and 300 mg/kg) by oral gavage for seven days before being treated with 250 mg/kg APAP. Sever liver injury was exerted at 24 h post-APAP and hepatotoxicity was assessed...
April 21, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28429777/interleukin-6-increases-the-expression-and-activity-of-insulin-degrading-enzyme
#6
Mirian A Kurauti, José M Costa-Júnior, Sandra M Ferreira, Gustavo J Santos, Carlos H G Sponton, Everardo M Carneiro, Guilherme D Telles, Mara P T Chacon-Mikahil, Cláudia R Cavaglieri, Luiz F Rezende, Antonio C Boschero
Impairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and activity. IL-6 KO mice displayed lower insulin clearance in the liver and skeletal muscle, compared with wild type (WT), due to reduced IDE expression and activity. We also observed that after 3-h incubation, IL-6, 50 and 100 ng ml(-1), increased the expression of IDE in HEPG2 and C2C12 cells, respectively...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428135/the-immunotoxicological-pattern-of-subchronic-and-chronic-benzene-exposure-in-rats
#7
Alexander V Karaulov, Irina V Mikhaylova, Alexander I Smolyagin, Viktor M Boev, Alexandra Kalogeraki, Aristides M Tsatsakis, Ayse Basak Engin
Exposure to benzene and its inevitable metabolites can result in deleterious effects on human health, including lymphocytopenia, hematotoxicity and cancer. However, the duration of exposure might alter the effects including immune consequences. The aim of this study was to determine whether benzene could modulate lymphocyte proliferation induced by the T cell mitogen concanavalin A, in rats, at different exposure durations. 386 Wistar rats were assigned into control and treatment groups which was subdivided into groups for 45, 90 and 135days for 0,6mL/kg of drinking water mixed benzene treatment...
April 17, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28428016/the-role-of-low-level-laser-therapy-on-neuropathic-pain-relief-and-interleukin-6-expression-following-spinal-cord-injury-an-experimental-study
#8
Negin Mojarad, Atousa Janzadeh, Mahmoud Yousefifard, Farinaz Nasirinezhad
INTRODUCTION: The effect of Low Level Laser Therapy (LLLT) as a non-invasive treatment of spinal cord injury (SCI) is still under investigation. Therefore, the present study aimed to evaluate the effectiveness of LLLT on neuropathic pain and interleukin-6 (IL-6) expression following SCI in male rats. METHODS: 46 adult male rats were divided into 5 groups of control, SCI, treatment with methylprednisolone sodium succinate (MPSS), 1-week LLLT and 2-week LLLT. Animals underwent behavioral evaluations for motor behavior, level of allodynia and hyperalgesia every week...
April 17, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28427412/lack-of-interleukin-13-receptor-%C3%AE-1-delays-the-loss-of-dopaminergic-neurons-during-chronic-stress
#9
Simone Mori, Shuei Sugama, William Nguyen, Tatiana Michel, M Germana Sanna, Manuel Sanchez-Alavez, Rigo Cintron-Colon, Gianluca Moroncini, Yoshihiko Kakinuma, Pamela Maher, Bruno Conti
BACKGROUND: The majority of Parkinson's disease (PD) cases are sporadic and idiopathic suggesting that this neurodegenerative disorder is the result of both environmental and genetic factors. Stress and neuroinflammation are among the factors being investigated for their possible contributions to PD. Experiments in rodents showed that severe chronic stress can reduce the number of dopaminergic neurons in the substantia nigra pars compacta (SNc); the same cells that are lost in PD. These actions are at least in part mediated by increased oxidative stress...
April 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28427134/-role-of-bone-marrow-tyrosine-kinase-on-chromosome-x-in-the-production-of-pro-inflammatory-cytokines-from-mouse-mononuclear-macrophages-raw264-7-induced-by-endotoxin-lipopolysaccharide-and-its-mechanism
#10
X Fang, Y Hu, Y Wang, S Liu, F Wang, X L Chen
Objective: To investigate the role of bone marrow tyrosine kinase on chromosome X (BMX) in the production of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) from mouse mononuclear-macrophages induced by endotoxin/lipopolysaccharide (LPS) and its related mechanism. Methods: Mouse mononuclear-macrophages RAW264.7 were inoculated in 6-well plates and routinely cultured for the following experiments. (1) Cells were collected and divided into blank control group, LPS control group, and 75, 750, 7 500, 75 000 nmol/L BMX-IN-1 pretreatment groups according to the random number table, with 8 wells in each group...
April 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28426339/fasting-levels-of-insulin-and-amylin-after-acute-pancreatitis-are-associated-with-pro-inflammatory-cytokines
#11
Nicola A Gillies, Sayali A Pendharkar, Ruma G Singh, John A Windsor, Madhav Bhatia, Maxim S Petrov
BACKGROUND: The prevalence of metabolic diseases continues to rise worldwide, with a growing recognition of metabolic dysregulation after acute inflammatory diseases such as acute pancreatitis (AP). Adipokines and cytokines play an important role in metabolism and the course of AP, but there is a paucity of research investigating their relationship with pancreatic hormones after AP. This study aimed to explore associations between pancreatic hormones with adipokines and cytokines to provide insights into the pathophysiology of altered pancreatic hormone secretion following AP...
April 20, 2017: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28425576/bone-marrow-adipose-and-lung-tissue-derived-murine-mesenchymal-stromal-cells-release-different-mediators-and-differentially-affect-airway-and-lung-parenchyma-in-experimental-asthma
#12
Soraia C Abreu, Mariana A Antunes, Debora G Xisto, Fernanda F Cruz, Vivian C Branco, Elga Bandeira, Jamil Zola Kitoko, Almair F de Araújo, Ludmilla Dellatorre-Texeira, Priscilla C Olsen, Daniel J Weiss, Bruno L Diaz, Marcelo M Morales, Patricia R M Rocco
Mesenchymal stromal cells (MSCs) from different sources have differential effects on lung injury. To compare the effects of murine MSCs from bone marrow (BM), adipose tissue (AD), and lung tissue (LUNG) on inflammatory and remodeling processes in experimental allergic asthma, female C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) or saline (C). Twenty-four hours after the last challenge, mice received either saline (50 µl, SAL), BM-MSCs, AD-MSCs, or LUNG-MSCs (10(5) cells per mouse in 50 µl total volume) intratracheally...
April 20, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28425113/environmental-perfluorooctane-sulfonate-exposure-drives-t-cell-activation-in-bottlenose-dolphins
#13
Adam C Soloff, Bethany Jacobs Wolf, Natasha D White, Derek Muir, Sean Courtney, Gary Hardiman, Gregory D Bossart, Patricia A Fair
Perfluoroalkyl acids (PFAAs) are highly stable compounds that have been associated with immunotoxicity in epidemiologic studies and experimental rodent models. Lengthy half-lives and resistance to environmental degradation result in bioaccumulation of PFAAs in humans and wildlife. Perfluorooctane sulfonate (PFOS), the most prevalent PFAA detected within the environment, is found at high levels in occupationally exposed humans. We have monitored the environmental exposure of dolphins in the Charleston, SC region for over 10 years and levels of PFAAs, and PFOS in particular, were significantly elevated...
April 19, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28424686/mucosal-and-systemic-immune-responses-to-influenza-h7n9-antigen-ha1-2-co-delivered-intranasally-with-flagellin-or-polyethyleneimine-in-mice-and-chickens
#14
Li Song, Dan Xiong, Hongqin Song, Lili Wu, Meihua Zhang, Xilong Kang, Zhiming Pan, Xinan Jiao
Consecutive cases of human infection with H7N9 influenza viruses since 2013 in China have prompted efforts to develop an effective treatment. Subunit vaccines introduced by intranasal administration can block an infection at its primary site; flagellin (fliC) and polyethyleneimine (PEI) have been shown to be potent adjuvants. We previously generated the hemagglutinin (HA)1-2-fliC fusion protein consisting of the globular head domain (HA1-2; amino acids 62-284) of HA fused with Salmonella typhimurium fliC. In the present study, we investigated its effectiveness of both flagellin and PEI as mucosal adjuvants for the H7N9 influenza subunit vaccine...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28424593/phospholipase-a2-of-peroxiredoxin-6-plays-a-critical-role-in-cerebral-ischemia-reperfusion-inflammatory-injury
#15
Yu Shanshan, Jiang Beibei, Tan Li, Gao Minna, Lei Shipeng, Peng Li, Zhao Yong
Microglia-mediated inflammation is an important step in the progression of cerebral ischemia/reperfusion injury and the associated production of receptors of immunomoudulation, including Toll-like receptors (TLRs). Peroxiredoxin 6 (Prdx6) has been demonstrated as the endogenous antioxidant protein for its peroxidase properties. However, the role of the independent phospholipase A2 (iPLA2) activity of Prdx6 in stroke has not been well studied. In this study, we evaluated whether blocking the calcium-iPLA2 activity of Prdx6 using siRNA and inhibitors (1-hexadecyl-3-(trifluoroethgl)-sn-glycerol-2 phosphomethanol, MJ33) would have a critical effect on inflammatory brain damage...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28424066/short-term-exposure-to-pm2-5-and-vanadium-and-changes-in-asthma-gene-dna-methylation-and-lung-function-decrements-among-urban-children
#16
Kyung Hwa Jung, David Torrone, Stephanie Lovinsky-Desir, Matthew Perzanowski, Joshua Bautista, Jacqueline R Jezioro, Lori Hoepner, Jamie Ross, Frederica P Perera, Steven N Chillrud, Rachel L Miller
BACKGROUND: Both short and long-term exposure to traffic-related air pollutants have been associated with asthma and reduced lung function. We hypothesized that short-term indoor exposure to fine particulate matter <2.5 μm (PM2.5) and vanadium (V) would be associated with altered buccal cell DNA methylation of targeted asthma genes and decreased lung function among urban children in a nested subcohort of African American and Dominican children. METHODS: Six day integrated levels of air pollutants were measured from children's homes (age 9-14; n = 163), repeated 6 months later (n = 98)...
April 19, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28423301/risankizumab-versus-ustekinumab-for-moderate-to-severe-plaque-psoriasis
#17
Kim A Papp, Andrew Blauvelt, Michael Bukhalo, Melinda Gooderham, James Krueger, Jean-Philippe Lacour, Alan Menter, Sandra Philipp, Howard Sofen, Stephen Tyring, Beate R Berner, Sudha Visvanathan, Chandrasena Pamulapati, Nathan Bennett, Mary Flack, Paul Scholl, Steven J Padula
Background Interleukin-23 is thought to be critical to the pathogenesis of psoriasis. We compared risankizumab (BI 655066), a humanized IgG1 monoclonal antibody that inhibits interleukin-23 by specifically targeting the p19 subunit and thus prevents interleukin-23 signaling, and ustekinumab, an interleukin-12 and interleukin-23 inhibitor, in patients with moderate-to-severe plaque psoriasis. Methods We randomly assigned a total of 166 patients to receive subcutaneous injections of risankizumab (a single 18-mg dose at week 0 or 90-mg or 180-mg doses at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, according to body weight, at weeks 0, 4, and 16)...
April 20, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28423239/a-novel-jak-inhibitor-jte-052-reduces-skin-inflammation-and-ameliorates-chronic-dermatitis-in-rodent-models-comparison-with-conventional-therapeutic-agents
#18
Atsuo Tanimoto, Yuichi Shinozaki, Yasuo Yamamoto, Yoshiaki Katsuda, Eriko Riya, Kaoru Toyoda, Kochi Kakimoto, Yukari Kimoto, Wataru Amano, Noriko Konishi, Mikio Hayashi
Janus kinases (JAKs) are required for several inflammatory cytokine signaling pathways and are implicated in the pathogenesis of chronic dermatitis, including atopic dermatitis and psoriasis. JAK inhibitors are therefore promising therapeutic candidates for chronic dermatitis. In this study, we evaluated the effects of the novel JAK inhibitor JTE-052 on inflammatory responses associated with chronic dermatitis, and compared its profile with those of conventional therapeutic agents in rodent models of chronic dermatitis...
April 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28421429/reslizumab-in-eosinophilic-asthma-a-review
#19
Emma D Deeks, Guy Brusselle
Reslizumab (Cinqaero(®); Cinqair(®)) is a humanized monoclonal antibody against interleukin-5 (IL-5), a cytokine mediator of eosinophilic airway inflammation. Reslizumab is indicated as an add-on treatment for severe eosinophilic asthma in adults, on the basis of data from the BREATH phase III clinical trial programme. In three double-blind BREATH studies of up to 52 weeks' duration, adding intravenous reslizumab (3 mg/kg, once every 4 weeks) to the current asthma therapy of patients (aged 12-75 years) with eosinophilic asthma inadequately controlled with inhaled corticosteroids resulted in significant reductions in clinical asthma exacerbation frequency and significant improvements in lung function, asthma control and health-related quality of life relative to adding placebo...
April 18, 2017: Drugs
https://www.readbyqxmd.com/read/28420813/establishment-of-cell-lines-from-adult-t-cell-leukemia-cells-dependent-on-negatively-charged-polymers
#20
Yoshitoyo Kagami, Susumu Uchiyama, Harumi Kato, Yasutaka Okada, Masao Seto, Tomohiro Kinoshita
Growing adult T-cell leukemia/lymphoma (ATLL) cells in vitro is difficult. Here, we examined the effects of static electricity in the culture medium on the proliferation of ATLL cells. Six out of 10 ATLL cells did not proliferate in vitro and thus had to be cultured in a medium containing negatively charged polymers. In the presence of poly-γ-glutamic acid (PGA) or chondroitin sulfate (CDR), cell lines (HKOX3-PGA, HKOX3-CDR) were established from the same single ATLL case using interleukin (IL)-2, IL-4, and feeder cells expressing OX40L (OX40L(+)HK)...
April 18, 2017: Journal of Clinical and Experimental Hematopathology: JCEH
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