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TNF alpha antagonists

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https://www.readbyqxmd.com/read/28422491/discovery-of-novel-ligands-for-tnf-%C3%AE-and-tnf-receptor-1-through-structure-based-virtual-screening-and-biological-assay
#1
Si Chen, Zhiwei Feng, Yun Wang, Shifan Ma, Ziheng Hu, Peng Yang, Yifeng Chai, Xiang-Qun Sean Xie
Tumor Necrosis Factor alpha (TNF-α) is overexpressed in various diseases, and it has been a validated therapeutic target for autoimmune diseases. All therapeutics currently used targeting TNF-α are biomacromolecules, and limited numbers of TNF-α chemical inhibitors have been reported, which makes the identification of small molecule alternatives in urgent need. Recent studies mainly focused on identifying small molecules that directly bind to TNF-α or TNF receptor-1 (TNFR1), and/or inhibit the interaction between TNF-α and TNFR1, and/or regulate related signaling pathways...
April 19, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28412968/interleukin-1-primes-human-mesenchymal-stem-cells-towards-an-anti-inflammatory-and-pro-trophic-phenotype-in-vitro
#2
Elena Redondo-Castro, Catriona Cunningham, Jonjo Miller, Licia Martuscelli, Sarah Aoulad-Ali, Nancy J Rothwell, Cay M Kielty, Stuart M Allan, Emmanuel Pinteaux
BACKGROUND: Inflammation is a key contributor to central nervous system (CNS) injury such as stroke, and is a major target for therapeutic intervention. Effective treatments for CNS injuries are limited and applicable to only a minority of patients. Stem cell-based therapies are increasingly considered for the treatment of CNS disease, because they can be used as in-situ regulators of inflammation, and improve tissue repair and recovery. One promising option is the use of bone marrow-derived mesenchymal stem cells (MSCs), which can secrete anti-inflammatory and trophic factors, can migrate towards inflamed and injured sites or can be implanted locally...
April 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28405087/leukocytoclastic-vasculitis-drug-reaction-to-certolizumab-pegol
#3
Meghan Woody, Donald Warren, Laura Speck, Julie Jackson
Tumor necrosis factor (TNF)-alpha antagonists are a common treatment modality for autoimmune disorders, but their use can be associated with many side effects, including various dermatologic conditions. Certolizumab pegol, a newer TNF antagonist that lacks the Fc portion of the IgG antibody, has recently been approved to treat psoriatic arthritis, rheumatoid arthritis, and Crohn's disease. Though other TNF antagonists have been associated with leukocytoclastic vasculitis, this finding has not yet been reported with certolizumab pegol...
April 2017: Proceedings of the Baylor University Medical Center
https://www.readbyqxmd.com/read/28395930/acetylcholine-attenuated-tnf-%C3%AE-induced-intracellular-ca-2-overload-by-inhibiting-the-formation-of-the-ncx1-trpc3-ip3r1-complex-in-human-umbilical-vein-endothelial-cells
#4
Ming Zhao, Hang-Huan Jia, Long-Zhu Liu, Xue-Yuan Bi, Man Xu, Xiao-Jiang Yu, Xi He, Wei-Jin Zang
The endoplasmic reticulum (ER) forms discrete junctions with the plasma membrane (PM) that play a critical role in the regulation of Ca(2+) signaling during cellular bioenergetics, apoptosis and autophagy. We have previously confirmed that acetylcholine can inhibit ER stress and apoptosis after inflammatory injury. However, limited research has focused on the effects of acetylcholine on ER-PM junctions. In this work, we evaluated the structure and function of the supramolecular sodium-calcium exchanger 1 (NCX1)-transient receptor potential canonical 3 (TRPC3)-inositol 1,4,5-trisphosphate receptor 1 (IP3R1) complex, which is involved in regulating Ca(2+) homeostasis during inflammatory injury...
April 7, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28392361/dexmedetomidine-confers-neuroprotection-against-transient-global-cerebral-ischemia-reperfusion-injury-in-rats-by-inhibiting-inflammation-through-inactivation-of-the-tlr-4-nf-%C3%AE%C2%BAb-pathway
#5
Eugene Kim, Hyun-Chang Kim, Seungmi Lee, Ho-Geol Ryu, Yong-Hee Park, Jun Hyun Kim, Young-Jin Lim, Hee-Pyoung Park
Dexmedetomidine (DXM) has anti-inflammatory effects, which is considered an important mechanism of DXM-induced neuroprotection from cerebral ischemia/reperfusion injury. We determined whether the anti-inflammatory effects of DXM are associated with inhibition of the toll-like receptor (TLR)-4/nuclear factor kappa B (NF-κB) pathway in a rat model of transient global cerebral ischemia/reperfusion injury. Fifty rats were randomly assigned to one of five groups (10 rats/group): Group S received no treatment; Group C underwent transient global ischemia (10min); Group D received DXM 30min before ischemia; Group R received resatorvid, a selective TLR-4 antagonist, 30min before ischemia; and Group RD received resatorvid and DXM 30min before ischemia...
April 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28386270/fimasartan-ameliorates-nonalcoholic-fatty-liver-disease-through-ppar%C3%AE-regulation-in-hyperlipidemic-and-hypertensive-conditions
#6
Yong-Jik Lee, Yoo-Na Jang, Yoon-Mi Han, Hyun-Min Kim, Jong-Min Jeong, Hong Seog Seo
To investigate the effects of fimasartan on nonalcoholic fatty liver disease in hyperlipidemic and hypertensive conditions, the levels of biomarkers related to fatty acid metabolism were determined in HepG2 and differentiated 3T3-L1 cells treated by high fatty acid and liver and visceral fat tissue samples of spontaneously hypertensive rats (SHRs) given high-fat diet. In HepG2 cells and liver tissues, fimasartan was shown to increase the protein levels of peroxisome proliferator-activated receptor delta (PPARδ), phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylated acetyl-CoA carboxylase (p-ACC), malonyl-CoA decarboxylase (MCD), medium chain acyl-CoA dehydrogenase (MCAD), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and it led to a decrease in the protein levels of 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSDH1), fatty acid synthase (FAS), and tumor necrosis factor-alpha (TNF-α)...
2017: PPAR Research
https://www.readbyqxmd.com/read/28382926/aldosterone-induces-inflammatory-cytokines-in-penile-corpus-cavernosum-by-activating-the-nf-%C3%AE%C2%BAb-pathway
#7
Fei Wu, Zu-Quan Xiong, Shan-Hua Mao, Ji-Meng Hu, Jian-Qing Wang, Hao-Wen Jiang, Qiang Ding
Emerging evidence indicates that aldosterone and mineralocorticoid receptors (MRs) are associated with the pathogenesis of erectile dysfunction. However, the molecular mechanisms remain largely unknown. In this study, freshly isolated penile corpus cavernosum tissue from rats was treated with aldosterone, with or without MRs inhibitors. Nuclear factor (NF)-kappa B (NF-κB) activity was evaluated by real-time quantitative PCR, luciferase assay, and immunoblot. The results demonstrated that mRNA levels of the NF-κB target genes, including inhibitor of NF-κB alpha (IκB-α), NF-κB1, tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6), were higher after aldosterone treatment...
April 4, 2017: Asian Journal of Andrology
https://www.readbyqxmd.com/read/28365861/tnf-%C3%AE-tnfr1-signaling-is-required-for-the-full-expression-of-acute-and-chronic-itch-in-mice-via-peripheral-and-central-mechanisms
#8
Xiuhua Miao, Ya Huang, Teng-Teng Liu, Ran Guo, Bing Wang, Xue-Long Wang, Li-Hua Chen, Yan Zhou, Ru-Rong Ji, Tong Liu
Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha (TNF-α) and its receptors TNF receptor subtype-1 (TNFR1) and TNFR2 in acute and chronic itch in mice. Compared to wild-type (WT) mice, TNFR1-knockout (TNFR1-KO) and TNFR1/R2 double-KO (DKO), but not TNFR2-KO mice, exhibited reduced acute itch induced by compound 48/80 and chloroquine (CQ). Application of the TNF-synthesis inhibitor thalidomide and the TNF-α antagonist etanercept dose-dependently suppressed acute itch...
April 1, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28303105/caloric-restriction-is-more-efficient-than-physical-exercise-to-protect-from-cisplatin-nephrotoxicity-via-ppar-alpha-activation
#9
Gabriel R Estrela, Frederick Wasinski, Rogério O Batista, Meire I Hiyane, Raphael J F Felizardo, Flavia Cunha, Danilo C de Almeida, Denise M A C Malheiros, Niels O S Câmara, Carlos C Barros, Michael Bader, Ronaldo C Araujo
The antineoplastic drug cisplatin promotes renal injury, which limits its use. Protocols that reduce renal cisplatin toxicity will allow higher doses to be used in cisplatin treatment. Here, we compare physical exercise and caloric restriction (CR) as protocols to reduce cisplatin renal injury in mice. Male C57BL/6 were divided into four groups: Control, cisplatin, exercise + cisplatin, and 30% CR + cisplatin. Animals were injected with a single dose of cisplatin (20 mg/kg i.p.) and sacrificed 96 h after injection...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28286061/tnf-alpha-antagonist-and-vascular-inflammation-in-patients-with-psoriasis-vulgaris-a-randomized-placebo-controlled-study
#10
Robert Bissonnette, François Harel, James G Krueger, Marie-Claude Guertin, Malorie Chabot-Blanchet, Juana Gonzalez, Catherine Maari, Isabelle Delorme, Charles W Lynde, Jean-Claude Tardif
BACKGROUND: Vascular inflammation is increased in patients with psoriasis. PURPOSE: This randomized, double-blind, multicenter study evaluated the effects of the tumor necrosis factor alpha (TNF-α) antagonist adalimumab on vascular inflammation in patients with psoriasis. METHOD: 107 patients were randomized (1:1) to receive adalimumab for 52 weeks OR placebo for 16 weeks followed by adalimumab for 52 weeks. Vascular inflammation was assessed with positron emission tomography-computed tomography...
March 9, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28283819/neurological-complications-of-beh%C3%A3-et-s-syndrome
#11
D P Kidd
In this review of the neurological complications of Behçet's syndrome, the clinical features and epidemiology of the systemic disease are summarised before a discussion of the neurological syndromes which may develop is made. Neurological involvement occurs in 9% of cases, and is equally prevalent in each geographical area. Vascular complications occur in 14%, in whom thrombosis of the venous sinuses or cerebral veins occurs, and intracranial hypertension, venous infarction and parenchymal haemorrhage may develop...
March 10, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28272203/sarcoidosis-associated-with-infliximab-therapy-in-ulcerative-colitis-a-case-report
#12
Georgiana-Emmanuela Gîlcă, Smaranda Diaconescu, Gheorghe Gh Bălan, Oana Timofte, Gabriela Ştefănescu
RATIONALE: Although immunomodulatory therapy has been clearly stated as an important landmark in treatment of ulcerative colitis, significantly improving the quality of life for patients with inflammatory bowel disease, there are several aspects to be considered regarding the possible side-effects of anti-TNF alpha agents. In spite of a good safety profile, biologic TNF antagonists may induce paradoxical inflammation, which can manifest as sarcoid-like granulomatosis, consisting of noncaseating granulomas in the affected organs...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28248533/the-effect-of-apelin-on-the-functions-of-peritoneal-macrophages
#13
V N Izgüt-Uysal, B Gemici, I Birsen, N Acar, I Üstünel
Apelin, the endogenous ligand of the G protein-coupled receptor (APJ), plays an important role in the physiological response to homeostatic perturbations. The aim of the present study was to investigate the effect of apelin on the functions of peritoneal macrophages. A double staining immunofluorescence technique was used to determine the expression of APJ in peritoneal macrophages. Rat peritoneal macrophages were randomly divided into three groups: control, apelin and apelin+F13A. A significant decrease in phagocytic and chemotactic activity of peritoneal macrophages resulted when the macrophages were incubated with [Pry(1)]-Apelin-13 (10 ng/ml)...
February 28, 2017: Physiological Research
https://www.readbyqxmd.com/read/28225051/low-muscle-mass-at-initiation-of-anti-tnf-therapy-for-inflammatory-bowel-disease-is-associated-with-early-treatment-failure-a-retrospective-analysis
#14
D Q Holt, P Varma, B J G Strauss, A S Rajadurai, G T Moore
BACKGROUND/OBJECTIVES: Delayed treatment failure occurs in a significant proportion of inflammatory bowel disease (IBD) patients treated with tumor necrosis factor-alpha (TNF) antagonists. Identification of predictors of loss of response (LOR) may help to optimize therapy. We sought to determine whether body composition parameters at the commencement of anti-TNF therapy were associated with earlier treatment failure. SUBJECTS/METHODS: A retrospective cohort study was performed on 68 patients who had undergone cross-sectional abdominal imaging coincident with the commencement of anti-TNF drugs...
February 22, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28219695/inhibitory-effects-of-dynorphin-3-14-on-the-lipopolysaccharide-induced-toll-like-receptor-4-signalling-pathway
#15
Siti Sarah Fazalul Rahiman, Michael Morgan, Paul Gray, Paul Nicholas Shaw, Peter John Cabot
Dynorphin 1-17 (DYN 1-17) is biotransformed rapidly to a range of fragments in rodent inflamed tissue with dynorphin 3-14 (DYN 3-14) being the most stable and prevalent. DYN 1-17 has been shown previously to be involved in the regulation of inflammatory response following tissue injury, in which the biotransformation fragments of DYN 1-17 may possess similar features. This study investigated the effects of DYN 3-14 on lipopolysaccharide (LPS)-induced nuclear factor-kappaB/p65 (NF-κB/p65) nuclear translocation and the release of pro-inflammatory cytokines interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in differentiated THP-1 cells...
February 20, 2017: Peptides
https://www.readbyqxmd.com/read/28211161/psoriasis-and-psoriasiform-eruptions-in-pediatric-patients-with-inflammatory-bowel-disease-treated-with-anti-tumor-necrosis-factor-alpha-agents
#16
Joshua B Eickstaedt, Luke Killpack, Jeanne Tung, Dawn Davis, Jennifer L Hand, Megha M Tollefson
BACKGROUND: Anti-tumor necrosis factor alpha (TNF-α) agents are used to treat a variety of autoimmune and inflammatory conditions, including psoriasis. Paradoxically, numerous reports have documented new-onset or exacerbation of psoriasis or psoriasiform skin lesions (PSO) in patients treated with these agents for conditions other than PSO-particularly in adults with inflammatory bowel disease (IBD). Not much is known regarding similar cases in children. METHODS: A retrospective chart review was performed on children younger than 19 years of age with IBD seen at the Mayo Clinic between 2003 and 2015 who developed new-onset or recurrent PSO while undergoing anti-TNF-α therapy...
February 17, 2017: Pediatric Dermatology
https://www.readbyqxmd.com/read/28199343/long-term-treatment-with-abatacept-or-tocilizumab-does-not-increase-epstein-barr-virus-load-in-patients-with-rheumatoid-arthritis-a-three-years-retrospective-study
#17
Nathalie Balandraud, Gaetan Texier, Emmanuel Massy, Olivier Muis-Pistor, Marielle Martin, Isabelle Auger, Marie-Caroline Guzian, Sandrine Guis, Thao Pham, Jean Roudier
BACKGROUND: Epstein-Barr Virus (EBV) is a widely disseminated lymphotropic herpes virus implicated in benign and malignant disorders. In transplant patients, immunosuppressive drugs (cyclosporine) diminish control of EBV replication, potentially leading to lymphoproliferative disorders (LPD). Rheumatoid arthritis (RA) patients have impaired control of EBV infection and have EBV load ten times higher than controls. As post transplant patients, patients with RA have increased risk of developing lymphomas...
2017: PloS One
https://www.readbyqxmd.com/read/28177670/effect-of-vitamin-d-on-isoprenaline-induced-myocardial-infarction-in-rats-possible-role-of-peroxisome-proliferator-activated-receptor-%C3%A9-ppar-%C3%A9
#18
Ola Ahmed El-Gohary, Mona Maher Allam
Infarct-like lesion induced by isoprenaline is a well-known model to study myocardial infarction (MI). Vitamin D has been shown to have anti-inflammatory and antioxidant effects. Recent studies highlighted cross talk between vitamin D and peroxisome proliferator-activated receptor gamma (PPAR- ɣ). The present study was designed to investigate the effect of pretreatment with vitamin D on the isoprenaline-induced infarct-like lesion in rats and the role of PPAR- ɣ as a novel mechanism in vitamin D-mediated cardio protective effect...
January 22, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28131783/antihyperalgesic-effect-of-cb1-receptor-activation-involves-the-modulation-of-p2x3-receptor-in-the-primary-afferent-neuron
#19
Maria Cláudia Gonçalves Oliveira-Fusaro, Cristiane Isabel Silva Zanoni, Gilson Gonçalves Dos Santos, Luis Paulo Manzo, Dionéia Araldi, Ivan José Magayewski Bonet, Cláudia Herrera Tambeli, Elayne Vieira Dias, Carlos Amilcar Parada
Cannabinoid system is a potential target for pain control. Cannabinoid receptor 1 (CB1) activation play a role in the analgesic effect of cannabinoids once it is expressed in primary afferent neurons. This study investigates whether the anti-hyperalgesic effect of CB1 receptor activation involves P2X3 receptor in primary afferent neurons. Mechanical hyperalgesia was evaluated by electronic von Frey test. Cannabinoid effect was evaluated using anandamide or ACEA, a non-selective or a selective CB1 receptor agonists, respectively; AM251, a CB1 receptor antagonist, and antisense ODN for CB1 receptor...
January 25, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28122130/peripheral-cytokine-and-chemokine-alterations-in-depression-a-meta-analysis-of-82-studies
#20
C A Köhler, T H Freitas, M Maes, N Q de Andrade, C S Liu, B S Fernandes, B Stubbs, M Solmi, N Veronese, N Herrmann, C L Raison, B J Miller, K L Lanctôt, A F Carvalho
OBJECTIVE: To conduct a systematic review and meta-analysis of studies that measured cytokine and chemokine levels in individuals with major depressive disorder (MDD) compared to healthy controls (HCs). METHOD: The PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched up until May 30, 2016. Effect sizes were estimated with random-effects models. RESULT: Eighty-two studies comprising 3212 participants with MDD and 2798 HCs met inclusion criteria...
May 2017: Acta Psychiatrica Scandinavica
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