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https://www.readbyqxmd.com/read/28530838/an-innovative-high-throughput-screening-approach-for-discovery-of-small-molecules-that-inhibit-tnf-receptors
#1
Chih Hung Lo, Nagamani Vunnam, Andrew K Lewis, Ting-Lan Chiu, Benjamin E Brummel, Tory M Schaaf, Benjamin D Grant, Prachi Bawaskar, David D Thomas, Jonathan N Sachs
Tumor necrosis factor receptor 1 (TNFR1) is a transmembrane receptor that binds tumor necrosis factor or lymphotoxin-alpha and plays a critical role in regulating the inflammatory response. Upregulation of these ligands is associated with inflammatory and autoimmune diseases. Current treatments reduce symptoms by sequestering free ligands, but this can cause adverse side effects by unintentionally inhibiting ligand binding to off-target receptors. Hence, there is a need for new small molecules that specifically target the receptors, rather than the ligands...
May 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28514851/blood-brain-barrier-penetrating-biologic-tnf-%C3%AE-inhibitor-for-alzheimer-s-disease
#2
Rudy Chang, Jillian Knox, Jae Chang, Aram Derbedrossian, Vitaly Vasilevko, David Cribbs, Ruben J Boado, William M Pardridge, Rachita Sumbria
OBJECTIVE: Tumor necrosis factor alpha (TNF-α) driven processes are involved at multiple stages of Alzheimer's disease (AD) pathophysiology and disease progression. Biologic TNF-α inhibitors (TNFIs) are the most potent class of TNFIs but cannot be developed for AD since these macromolecules do not cross the blood-brain barrier (BBB). A BBB-penetrating TNFI was engineered by the fusion of the extracellular domain of the type II human TNF receptor (TNFR) to a chimeric monoclonal antibody (MAb) against the mouse transferrin receptor (TfR), designated as the cTfRMAb-TNFR fusion protein...
May 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28513838/the-emerging-role-of-npnt-in-tissue-injury-repair-and-bone-homeostasis
#3
REVIEW
Youqiang Sun, Vincent Kuek, Heng Qiu, Jennifer Tickner, Leilei Chen, Haibin Wang, Wei He, Jiake Xu
Nephronectin (NPNT), a highly conserved extracellular matrix protein, plays an important role in regulating cell adhesion, differentiation, spreading and survival. NPNT protein belongs to epidermal growth factor (EGF)-like superfamily and exhibits several common structural determinants; including EGF-like repeat domains, MAM domain (Meprin, A5 Protein, and Receptor Protein-Tyrosine Phosphatase µ), RGD motif (Arg-Gly-Asp) and a coiled-coil domain. It regulates integrins-mediated signaling pathways via the interaction of its RGD motif with integrin α8β1...
May 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28511952/lithium-ameliorates-lipopolysaccharide-induced-neurotoxicity-in-the-cortex-and-hippocampus-of-the-adult-rat-brain
#4
Muhammad Sohail Khan, Tahir Ali, Muhammad Noman Abid, Myeung Hoon Jo, Amjad Khan, Min Woo Kim, Gwang Ho Yoon, Eun Woo Cheon, Shafiq Ur Rehman, Myeong Ok Kim
Lithium an effective mood stabilizer, primary used in the treatment of bipolar disorders, has been reported as a protective agent in various neurological disorders. In this study, we examined the neuroprotective role of lithium chloride (LiCl) against lipopolysaccharide (LPS) in the cortex and hippocampus of the adult rat brain. We determined that LiCl -attenuated LPS-induced activated toll-like receptor 4 (TLR4) signalling and significantly reduced the nuclear factor-kB (NF-KB) translation factor and various other inflammatory mediators such as interleukin-1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α)...
May 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28511117/conditioned-medium-from-relapsing-remitting-multiple-sclerosis-patients-reduces-the-expression-and-release-of-inflammatory-cytokines-induced-by-lps-gingivalis-in-thp-1-and-mo3-13-cell-lines
#5
Patrizia Ballerini, Francesca Diomede, Nicola Petragnani, Simona Cicchitti, Ilaria Merciaro, Marcos F X B Cavalcanti, Oriana Trubiani
The present research was aimed at evaluating the effect of the conditioned medium (CM) from human periodontal ligament stem cells (hPDLSCs) obtained from healthy donors (hPDLSCs-CM) and from Relapsing-Remitting Multiple Sclerosis patients (RR-MS-CM) on inflammatory response induced by Porphyromonas gingivalis lipopolysaccharide (LPS-G) in a monocytoid human cell line (THP-1) and human oligodendrocyte cell line (MO3.13). Human periodontal ligament biopsies were carried out from control donor patients and selected RR-MS donors...
May 13, 2017: Cytokine
https://www.readbyqxmd.com/read/28487429/rationally-designed-tlr4-ligands-for-vaccine-adjuvant-discovery
#6
Kelsey A Gregg, Erin Harberts, Francesca M Gardner, Mark R Pelletier, Corinne Cayatte, Li Yu, Michael P McCarthy, Jason D Marshall, Robert K Ernst
Adjuvant properties of bacterial cell wall components like MPLA (monophosphoryl lipid A) are well described and have gained FDA approval for use in vaccines such as Cervarix. MPLA is the product of chemically modified lipooligosaccharide (LOS), altered to diminish toxic proinflammatory effects while retaining adequate immunogenicity. Despite the virtually unlimited number of potential sources among bacterial strains, the number of useable compounds within this promising class of adjuvants are few. We have developed bacterial enzymatic combinatorial chemistry (BECC) as a method to generate rationally designed, functionally diverse lipid A...
May 9, 2017: MBio
https://www.readbyqxmd.com/read/28482409/-protective-effect-of-glycogen-synthase-kinase-3%C3%AE-inhibition-via-peroxisome-proliferator-activated-receptor-alpha-activation-in-mice-with-acute-liver-failure
#7
H B Shi, H L Shi, X Y Zhang, D X Chen, Z P Duan, F Ren
Objective: To investigate the role of the glycogen synthase kinase 3β (GSK3β) and the peroxisome proliferator-activated receptor alpha (PPARα) signaling pathway in acute liver failure and related mechanisms in a mouse model of acute liver failure induced by D-galactosamine/lipopolysaccharide (D-GalN/LPS). Methods: C57BL/6 mice were given intraperitoneal injection of D-GalN/LPS to establish a mouse model of acute liver failure. SB216763 was used to inhibit the activity of GSK3β and PPARα siRNA was used to inhibit the expression of PPARα...
March 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28481289/interleukin-17a-promotes-lymphocytes-adhesion-and-induces-ccl2-and-cxcl1-release-from-brain-endothelial-cells
#8
Dagmara Weronika Wojkowska, Piotr Szpakowski, Andrzej Glabinski
The nature of the interaction between Th17 cells and the blood-brain barrier (BBB) is critical for the development of autoimmune inflammation in the central nervous system (CNS). Tumor necrosis factor alpha (TNF-α) or interleukin 17 (IL-17) stimulation is known to enhance the adherence of Th17 cells to the brain endothelium. The brain endothelial cells (bEnd.3) express Vascular cell adhesion molecule 1 (VCAM-1), the receptor responsible for inflammatory cell adhesion, which binds very late antigen 4 (VLA-4) on migrating effector lymphocytes at the early stage of brain inflammation...
May 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28479722/influence-of-capsaicin-on-inflammatory-cytokines-induced-by-lipopolysaccharide-in-myoblast-cells-under-in-vitro-environment
#9
Ke Shang, Touseef Amna, Musarat Amina, Nawal M Al-Musayeib, Salem S Al-Deyab, Inho Hwang
BACKGROUND: ellular damage initiated by reactive oxygen species (ROS) is the main cause of numerous severe diseases and therefore for this reason, the natural antioxidants have note worthy significance in human health. Capsaicin possesses noteworthy analgesic and anti-inflammatory properties. It also possesses healing effects for treatment of arthritis, diabetic neuropathy, gastric lesions, and cardiac excitability that is why it is incorporated in creams and gels. OBJECTIVE: The present study was carried out to estimate the in vitro antioxidant and ROS scavenging activities of capsaicin against muscle precursor cells...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28469598/involvement-of-the-bradykinin-b1-receptor-in-microglial-activation-in-vitro-and-in-vivo-studies
#10
Keren Asraf, Nofar Torika, Abraham Danon, Sigal Fleisher-Berkovich
The importance of brain inflammation to Alzheimer's disease (AD) pathogenesis has been accepted of late, with it currently being held that brain inflammation aggravates AD pathology. One important aspect of brain inflammation is the recruitment and activation of microglia, a process termed microgliosis. Kinins and bradykinin (BK), in particular, are major pro-inflammatory mediators in the periphery, although all of the factors comprising the kinin system have also been described in the brain. Moreover, it was shown that the amyloid β (Aβ) peptide (a component of AD plaques) enhances kinin secretion and activates BK receptors that can, in turn, stimulate Aβ production...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28465680/sex-differences-in-the-effect-of-resveratrol-on-dss-induced-colitis-in-mice
#11
Alexandra Wagnerova, Janka Babickova, Robert Liptak, Barbora Vlkova, Peter Celec, Roman Gardlik
Resveratrol is a natural polyphenol studied for its possible protective properties in inflammatory bowel diseases. Moreover, it has been shown to interact with estrogen receptors. In the present study, we aimed to investigate possible diverse effects of resveratrol on female and male mice in DSS-induced colitis. Thirty-seven C57BL/6 mice (21 female and 16 male) were divided into three groups for each sex. The first group received pure water (CTRL). The other two groups received 1.5% dextran sulfate sodium (DSS) to induce colitis from which one group was treated with resveratrol (DSS + RSV)...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28465254/activation-of-adenosine-a2a-receptor-signaling-regulates-the-expression-of-cytokines-associated-with-immunologic-dysfunction-in-btbr-t-itpr3-tf-j-mice
#12
Mushtaq A Ansari, Sabry M Attia, Ahmed Nadeem, Saleh A Bakheet, Mohammad Raish, Tajdar H Khan, Othman A Al-Shabanah, Sheikh F Ahmad
Autism spectrum disorder (ASD) is neurodevelopmental disorders characterized by stereotypical repetitive behavior, impaired social interaction, and deficits in communication. The BTBR T(+) Itpr3(tf)/J (BTBR) mice have been extensively used as an animal model of the ASD-like phenotype. Adenosine A2A receptors (A2ARs) are considered potential targets in the treatment of neurodegenerative diseases. In this study, we used the A2AR antagonist SCH 5826 (SCH) and the A2AR agonist CGS 21680 (CGS) to investigate the activation of A2AR signaling in immune cells...
April 30, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28456632/tumor-necrosis-factor-inhibits-spread-of-hepatitis-c-virus-among-liver-cells-independent-from-interferons
#13
Stephen M Laidlaw, Svetlana Marukian, Rachel H Gilmore, Siobhán B Cashman, Volodymyr Nechyporuk-Zloy, Charles M Rice, Lynn B Dustin
BACKGROUND & AIMS: Tumor necrosis factor (TNF) an inflammatory cytokine expressed by human fetal liver cells (HFLCs) following infection with cell culture-derived hepatitis C virus. TNF has been reported to increase entry of HCV pseudoparticles into hepatoma cells and inhibit signaling by interferon alpha (IFNA), but have no effect on replication of HCV RNA. We investigated the effects of TNF on HCV infection of and spread among Huh-7 hepatoma cells and primary HFLCs.  METHODS: Human hepatoma (Huh-7 and Huh-7...
April 26, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28455700/short-term-fructose-feeding-induces-inflammation-and-oxidative-stress-in-the-hippocampus-of-young-and-adult-rats
#14
Luisa Cigliano, Maria Stefania Spagnuolo, Raffaella Crescenzo, Rosa Cancelliere, Lucia Iannotta, Arianna Mazzoli, Giovanna Liverini, Susanna Iossa
The drastic increase in the consumption of fructose encouraged the research to focus on its effects on brain physio-pathology. Although young and adults differ largely by their metabolic and physiological profiles, most of the previous studies investigated brain disturbances induced by long-term fructose feeding in adults. Therefore, we investigated whether a short-term consumption of fructose (2 weeks) produces early increase in specific markers of inflammation and oxidative stress in the hippocampus of young and adult rats...
April 28, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28442041/cytokine-gene-expression-at-the-maternal-fetal-interface-after-somatic-cell-nuclear-transfer-pregnancies-in-small-ruminants
#15
Heloisa M Rutigliano, Amanda Wilhelm, Justin Hall, Bi Shi, Qinggang Meng, Rusty Stott, Thomas D Bunch, Kenneth L White, Christopher J Davies, Irina A Polejaeva
The present retrospective study investigated pregnancy rates, the incidence of pregnancy loss and large offspring syndrome (LOS) and immune-related gene expression of sheep and goat somatic cell nuclear transfer (SCNT) pregnancies. We hypothesised that significantly higher pregnancy losses observed in sheep compared with goat SCNT pregnancies are due to the increased amounts of T-helper 1 cytokines and proinflammatory mediators at the maternal-fetal interface. Sheep and goat SCNT pregnancies were generated using the same procedure...
April 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28441778/gene-expression-analysis-before-and-after-treatment-with-adalimumab-in-patients-with-ankylosing-spondylitis-identifies-molecular-pathways-associated-with-response-to-therapy
#16
Marzia Dolcino, Elisa Tinazzi, Andrea Pelosi, Giuseppe Patuzzo, Francesca Moretta, Claudio Lunardi, Antonio Puccetti
The etiology of Ankylosing spondylitis (AS) is still unknown and the identification of the involved molecular pathogenetic pathways is a current challenge in the study of the disease. Adalimumab (ADA), an anti-tumor necrosis factor (TNF)-alpha agent, is used in the treatment of AS. We aimed at identifying pathogenetic pathways modified by ADA in patients with a good response to the treatment. Gene expression analysis of Peripheral Blood Cells (PBC) from six responders and four not responder patients was performed before and after treatment...
April 24, 2017: Genes
https://www.readbyqxmd.com/read/28430654/alpha-ketoglutarate-suppresses-the-nf-%C3%AE%C2%BAb-mediated-inflammatory-pathway-and-enhances-the-pxr-regulated-detoxification-pathway
#17
Liuqin He, Huan Li, Niu Huang, Xihong Zhou, Junquan Tian, Tiejun Li, Jing Wu, Yanan Tian, Yulong Yin, Kang Yao
Alpha-ketoglutarate (AKG) is a critical nutritional factor in the maintenance of intestinal homeostasis. However, the relative mechanism of AKG has not been well understood. It was recently shown that the interaction between nuclear factor kappa B (NF-κB)-mediated inflammatory pathway and pregnane X receptor (PXR)-regulated detoxification pathway is a check and balance mechanism for keeping the homeostatic state of the intestine, preventing the onset of intestinal inflammation which may lead to cancer. In the current study we used lipopolysaccharide (LPS)-challenged piglet and intestinal porcine epithelial cells-J2 models to investigate the effects of dietary AKG supplementation on the intestinal immune system and PXR regulated target expression...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430652/inflammatory-factor-tnf-%C3%AE-promotes-the-growth-of-breast-cancer-via-the-positive-feedback-loop-of-tnfr1-nf-%C3%AE%C2%BAb-and-or-p38-p-stat3-hbxip-tnfr1
#18
Xiaoli Cai, Can Cao, Jiong Li, Fuquan Chen, Shuqin Zhang, Bowen Liu, Weiying Zhang, Xiaodong Zhang, Lihong Ye
In the connection between inflammation and cancer development, tumor necrosis factor-alpha (TNF-α) contributes to the tumorigenesis. However, the underlying mechanism remains poorly understood. In this study, we report that TNF-α enhances the growth of breast cancer through up-regulation of oncoprotein hepatitis B X-interacting protein (HBXIP). Our data showed that the levels of TNF-α were positively related to those of HBXIP in clinical breast cancer tissues. Moreover, TNF-α could up-regulate HBXIP in breast cancer cells...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429750/correlations-of-tnf-%C3%AE-gene-promoter-polymorphisms-with-the-risk-of-thymoma-associated-myasthenia-gravis-in-a-northern-chinese-han-population
#19
H-W Yang, P Lei, Y-C Xie, Z-L Han, D Li, S-H Wang, Z-L Sun
This study was performed with the aim to investigate the correlations of tumor necrosis factor-alpha (TNF-α) gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis (T-MG) in a northern Chinese Han population. Between June 2005 and June 2015, 305 MG patients (150 males and 155 females, MG group) and 293 healthy volunteers (negative control (NC) group) were enrolled in this study. Among the MG patients, there were 121 patients with thymoma-associated MG (T-MG group) and 184 without T-MG (NT-MG group)...
April 21, 2017: Cancer Gene Therapy
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
#20
Si Chen, Zhiwei Feng, Yun Wang, Shifan Ma, Ziheng Hu, Peng Yang, Yifeng Chai, Xiangqun Xie
Tumor necrosis factor α (TNF-α) is overexpressed in various diseases, and it has been a validated therapeutic target for autoimmune diseases. All therapeutics currently used to target TNF-α are biomacromolecules, and limited numbers of TNF-α chemical inhibitors have been reported, which makes the identification of small-molecule alternatives an urgent need. Recent studies have mainly focused on identifying small molecules that directly bind to TNF-α or TNF receptor-1 (TNFR1), inhibit the interaction between TNF-α and TNFR1, and/or regulate related signaling pathways...
May 11, 2017: Journal of Chemical Information and Modeling
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