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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
#1
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
#2
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
#3
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
#4
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/28414309/tumor-derived-fibulin-3-activates-pro-invasive-nf-%C3%AE%C2%BAb-signaling-in-glioblastoma-cells-and-their-microenvironment
#5
M S Nandhu, A Kwiatkowska, V Bhaskaran, J Hayes, B Hu, M S Viapiano
Molecular profiling of glioblastomas has revealed the presence of key signaling hubs that contribute to tumor progression and acquisition of resistance. One of these main signaling mechanisms is the nuclear factor-kappa B (NF-κB) pathway, which integrates multiple extracellular signals into transcriptional programs for tumor growth, invasion and maintenance of the tumor-initiating population. We show here that an extracellular protein released by glioblastoma cells, fibulin-3, drives oncogenic NF-κB in the tumor and increases NF-κB activation in peritumoral astrocytes...
April 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28412968/interleukin-1-primes-human-mesenchymal-stem-cells-towards-an-anti-inflammatory-and-pro-trophic-phenotype-in-vitro
#6
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/28396748/innate-immune-responses-induced-by-lipopolysaccharide-and-lipoteichoic-acid-in-primary-goat-mammary-epithelial-cells
#7
Omar Bulgari, Xianwen Dong, Alfred L Roca, Anna M Caroli, Juan J Loor
BACKGROUND: Innate immune responses induced by in vitro stimulation of primary mammary epithelial cells (MEC) using Gram-negative lipopolysaccharide (LPS) and Gram-positive lipoteichoic acid (LTA) bacterial cell wall components are well- characterized in bovine species. The objective of the current study was to characterize the downstream regulation of the inflammatory response induced by Toll-like receptors in primary goat MEC (pgMEC). We performed quantitative real-time RT-PCR (qPCR) to measure mRNA levels of 9 genes involved in transcriptional regulation or antibacterial activity: Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), prostaglandin-endoperoxide synthase 2 (PTGS2), interferon induced protein with tetratricopeptide repeats 3 (IFIT3), interferon regulatory factor 3 (IRF3), myeloid differentiation primary response 88 (MYD88), nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1), Toll interacting protein (TOLLIP), and lactoferrin (LTF)...
2017: Journal of Animal Science and Biotechnology
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
#8
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/28392436/an-oral-administration-of-a-recombinant-anti-tnf-fusion-protein-is-biologically-active-in-the-gut-promoting-regulatory-t-cells-results-of-a-phase-i-clinical-trial-using-a-novel-oral-anti-tnf-alpha-based-therapy
#9
Einat Almon, Tawfik Khoury, Ariel Drori, Svetlana Gingis-Velitski, Sari Alon, Raul Chertkoff, Mordechai Mushkat, Yoseph Shaaltiel, Yaron Ilan
BACKGROUND: An orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human IgG1 domain. Aim This study aim at determining the safety and the immune modulatory effect of an oral administration of PRX-106 in humans. METHODS: Three different doses (2, 8 or 16mg/day) of PRX-106 were orally administered for five consecutive days in 14 healthy volunteered participants...
April 6, 2017: Journal of Immunological Methods
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
#10
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/28391633/comparisons-of-cardioprotective-efficacy-between-fibroblast-growth-factor-21-and-dipeptidyl-peptidase-4-inhibitor-in-pre-diabetic-rats
#11
Pongpan Tanajak, Piangkwan Sa-Nguanmoo, Nattayaporn Apaijai, Xiaojie Wang, Guang Liang, Xiaokun Li, Chao Jiang, Siriporn C Chattipakorn, Nipon Chattipakorn
AIMS: Comparative efficacy between fibroblast growth factor 21 (FGF21) and vildagliptin on metabolic regulation, cardiac mitochondrial function, heart rate variability (HRV) and left ventricular (LV) function is not known. We hypothesized that FGF21 and vildagliptin share a similar efficacy in improving these parameters in high-fat diet (HFD) induced obese-insulin resistant rats. METHODS: Twenty-four male Wistar rats were fed with either a normal diet (ND) or a HFD for 12 weeks...
April 9, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28390866/activation-of-transforming-growth-factor-beta-1-signaling-in-gastric-cancer-associated-fibroblasts-increases-their-motility-via-expression-of-rhomboid-5-homolog-2-and-ability-to-induce-invasiveness-of-gastric-cancer-cells
#12
Takatsugu Ishimoto, Keisuke Miyake, Tannistha Nandi, Masakazu Yashiro, Nobuyuki Onishi, Kie Kyon Huang, Suling Joyce Lin, Ramnarayanan Kalpana, Su Ting Tay, Yuka Suzuki, Byoung Chul Cho, Daisuke Kuroda, Kota Arima, Daisuke Izumi, Masaaki Iwatsuki, Yoshifumi Baba, Eiji Oki, Masayuki Watanabe, Hideyuki Saya, Kosei Hirakawa, Hideo Baba, Patrick Tan
BACKGROUND & AIMS: Fibroblasts that interact with cancer cells are called cancer-associated fibroblasts (CAFs)-they promote progression of different tumor types. We investigated the characteristics and functions of CAFs in diffuse-type gastric cancers (DGCs) by analyzing features of their genome and gene expression patterns. METHODS: We isolated CAFs and adjacent non-cancer fibroblasts (NFs) from 110 GC tissues from patients who underwent gastrectomy in Japan from 2008 through 2016...
April 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28388655/functional-toll-like-receptor-tlr-2-polymorphisms-in-the-susceptibility-to-inflammatory-bowel-disease
#13
Helga Paula Török, Victor Bellon, Astrid Konrad, Martin Lacher, Laurian Tonenchi, Matthias Siebeck, Stephan Brand, Enrico Narciso De Toni
BACKGROUND: The recent genome-wide association studies (GWAS) in inflammatory bowel disease (IBD) suggest significant genetic overlap with complex mycobacterial diseases like tuberculosis or leprosy. TLR variants have previously been linked to susceptibility for mycobacterial diseases. Here we investigated the contribution to IBD risk of two TLR2 polymorphisms, the low-prevalence variant Arg753Gln and the GTn microsatellite repeat polymorphism in intron 2. We studied association with disease, possible correlations with phenotype and gene-gene interactions...
2017: PloS One
https://www.readbyqxmd.com/read/28388365/protective-effects-of-telmisartan-and-tempol-on-lipopolysaccharide-induced-cognitive-impairment-neuro-inflammation-and-amyloidogenesis-possible-role-of-brain-derived-neurotrophic-factor
#14
Waleed Abd-Elsalam Khallaf, Basim Messiha, Amira Abo-Youssef, Nesrine Salah El Dine El Sayed
Angiotensin II has pro-inflammatory and pro-oxidant potentials. We investigated the possible protective effects of the angiotensin receptor blocker telmisartan, compared with the superoxide scavenger tempol, on lipopolysaccharide (LPS)-induced cognitive decline and amyloidogenesis. Briefly, mice were allocated into a normal control group, an LPS control group, a tempol treatment group, and two telmisartan treatment groups. A behavioral study was conducted followed by a biochemical study via assessment of brain levels of beta amyloid (Aβ) and brain-derived neurotropic factor (BDNF) as amyloidogenesis and neuroplasticity markers, tumor necrosis factor-alpha (TNF-α), nitric oxide end products (NOx), neuronal and inducible nitric oxide synthase (nNOS and iNOS) as inflammatory markers, and superoxide dismutase (SOD), malondialdehyde (MDA), glutathione reduced (GSH) and nitrotyrosine (NT) as oxido-nitrosative stress markers...
April 7, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28386270/fimasartan-ameliorates-nonalcoholic-fatty-liver-disease-through-ppar%C3%AE-regulation-in-hyperlipidemic-and-hypertensive-conditions
#15
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/28385547/in-vitro-and-in-vivo-stimulation-of-toll-like-receptor-9-by-cpg-oligodeoxynucleotides-incorporated-into-polypod-like-dna-nanostructures
#16
Yosuke Takahashi, Tatsuoki Maezawa, Yuki Araie, Yuki Takahashi, Yoshinobu Takakura, Makiya Nishikawa
Cytosine-phosphate-guanine (CpG) DNA is known to increase the potency of vaccines. Here, in vitro and in vivo stimulation of Toll-like receptor 9 (TLR9) by CpG DNA incorporated into polypod-like DNA nanostructures was evaluated by measuring the levels of tumor necrosis factor alpha (TNF-α) released from macrophage-like RAW 264.7 cells and plasma interleukin (IL)-12p40 in vivo following intravenous injection into mice. Phosphodiester CpG1668 was selected as the CpG DNA, and tripodna and hexapodna, which were CpG1668-containing tripod and hexapod-like DNA nanostructures, respectively, were designed...
April 3, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28382926/aldosterone-induces-inflammatory-cytokines-in-penile-corpus-cavernosum-by-activating-the-nf-%C3%AE%C2%BAb-pathway
#17
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/28382862/inflammatory-bowel-disease-new-therapeutic-options-in-the-post-anti-tnf%C3%AE-era
#18
Miguel Jiménez Pérez, Raúl V Olmedo Martín, Víctor M Amo Trillo, Rocío González Gande
Inflammatory bowel diseasesare chronic bowel disorders the causes of which have not been fully elucidated,though they all sharean immunological basis. They have an important impact on both quality of life of the patient and on healthcare services. The incorporation of biological agents against tumour necrosis factor (TNF) alpha some 15 years ago represented a revolution in the management of patients with disease that did not respond to conventional treatment, enabling an overall improvement in the quality of life of many of these patients...
April 6, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28371137/proanthocyanidin-protects-against-cisplatin-induced-oxidative-liver-damage-through-inhibition-of-inflammation-and-nf-%C3%AE%C2%BA%C3%AE-tlr-4-pathway
#19
Nagla A El-Shitany, Basma Eid
Although cisplatin (CIS) is a highly effective anticancer drug, hepatotoxicity is one of the most common adverse effects associated with its use. Recently, reactive oxygen species (ROS) and inflammation are suggested to be key factors in the pathophysiology of CIS-induced acute liver damage. The aim of this study is to investigate the possible protective effect of proanthocyanidin (PRO) against CIS-induced acute hepatotoxicity. Rats were divided into four groups: 1, Control; 2, PRO; 3, CIS; and 4, PRO + CIS...
March 29, 2017: Environmental Toxicology
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
#20
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
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