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https://www.readbyqxmd.com/read/28647375/type-i-interferon-signalling-through-ifnar1-plays-a-deleterious-role-in-the-outcome-after-stroke
#1
Moses Zhang, Catherine E Downes, Connie H Y Wong, Kate M Brody, Pedro L Guio-Agulair, Jodee Gould, Robert Ates, Paul J Hertzog, Juliet M Taylor, Peter J Crack
Neuroinflammation contributes significantly to the pathophysiology of stroke. Here we test the hypothesis that the type I interferon receptor (IFNAR1) plays a critical role in neural injury after stroke by regulating the resultant pro-inflammatory environment. Wild-type and IFNAR1(-/-) primary murine neurons and glia were exposed to oxygen glucose deprivation (OGD) and cell viability was assessed. Transient cerebral ischemia/reperfusion injury was induced by mid-cerebral artery occlusion (MCAO) in wild-type and IFNAR1(-/-) and IFNAR2(-/-) mice in vivo, and infarct size, and molecular parameters measured...
June 21, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28622591/targeting-proinflammatory-cytokines-oxidative-stress-tgf-%C3%AE-1-and-stat-3-by-rosuvastatin-and-ubiquinone-to-ameliorate-trastuzumab-cardiotoxicity
#2
Ahmed M Kabel, Abeer A Elkhoely
The aim of this study was to assess the possible modulatory effects of rosuvastatin and/or ubiquinone on trastuzumab (TRZ)-induced cardiotoxicity in mice. One hundred and twenty mice were divided into six equal groups as follows: control group; TRZ group; TRZ+carboxymethyl cellulose group; TRZ+rosuvastatin group; TRZ+Ubiquinone group and TRZ+rosuvastatin+Ubiquinone group. Serum creatine kinase (CK-MB), lactate dehydrogenase (LDH), troponin I and N-terminal pro-B-type natriuretic peptide (NT-pro BNP) were measured...
June 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28608285/the-glp-1-analogue-lixisenatide-decreases-atherosclerosis-in-insulin-resistant-mice-by-modulating-macrophage-phenotype
#3
Ángela Vinué, Jorge Navarro, Andrea Herrero-Cervera, Marta García-Cubas, Irene Andrés-Blasco, Sergio Martínez-Hervás, José T Real, Juan F Ascaso, Herminia González-Navarro
AIMS/HYPOTHESIS: Recent clinical studies indicate that glucagon-like peptide-1 (GLP-1) analogues prevent acute cardiovascular events in type 2 diabetes mellitus but their mechanisms remain unknown. In the present study, the impact of GLP-1 analogues and their potential underlying molecular mechanisms in insulin resistance and atherosclerosis are investigated. METHODS: Atherosclerosis development was evaluated in Apoe (-/-) Irs2 (+/-) mice, a mouse model of insulin resistance, the metabolic syndrome and atherosclerosis, treated with the GLP-1 analogues lixisenatide or liraglutide...
June 12, 2017: Diabetologia
https://www.readbyqxmd.com/read/28593472/l-glutamine-in-vitro-modulates-some-immunomodulatory-properties-of-bone-marrow-mesenchymal-stem-cells
#4
Guilherme Galvão Dos Santos, Araceli Aparecida Hastreiter, Talita Sartori, Primavera Borelli, Ricardo Ambrósio Fock
Glutamine (GLUT) is a nonessential amino acid that can become conditionally essential under stress conditions, being able to act in the modulation of the immune responses. Mesenchymal stem cells (MSCs) are known to their capability in the modulation of immune responses through cell-cell contact and by the secretion of soluble factors. Considering that GLUT is an immunonutrient and little is known about the influence of GLUT on the capability of MSCs to modulate immune cells, this work aims to investigate how variations in GLUT concentrations in vitro could affect some immunomodulatory properties of MSCs...
June 7, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28579221/stat3-in-cancer-a-double-edged-sword
#5
Lidia Avalle, Annalisa Camporeale, Andrea Camperi, Valeria Poli
The transcription factor signal transducer and activator of transcription (STAT) 3 is activated downstream of cytokines, growth factors and oncogenes to mediate their functions under both physiological and pathological conditions. In particular, aberrant/unrestrained STAT3 activity is detected in a wide variety of tumors, driving multiple pro-oncogenic functions. For that, STAT3 is widely considered as an oncogene and is the object of intense translational studies. One of the distinctive features of this factor is however, its ability to elicit different and sometimes contrasting effects under different conditions...
May 31, 2017: Cytokine
https://www.readbyqxmd.com/read/28576409/phosphoproteome-and-transcription-factor-activity-profiling-identify-actions-of-the-anti-inflammatory-agent-utl-5g-in-lps-stimulated-raw-264-7-cells-including-disrupting-actin-remodeling-and-stat-3-activation
#6
Nicholas J Carruthers, Paul M Stemmer, Ben Chen, Frederick Valeriote, Xiaohua Gao, Subash C Guatam, Jiajiu Shaw
UTL-5g is a novel small-molecule TNF-alpha modulator. It reduces cisplatin-induced side effects by protecting kidney, liver, and platelets, thereby increasing tolerance for cisplatin. UTL-5g also reduces radiation-induced acute liver toxicity. The mechanism of action for UTL-5g is not clear at the present time. A phosphoproteomic analysis to a depth of 4943 phosphopeptides and a luminescence-based transcription factor activity assay were used to provide complementary analyses of signaling events that were disrupted by UTL-5g in RAW 264...
May 30, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28560450/upregulation-of-socs3-in-lung-cd4-t-cells-in-a-mouse-model-of-chronic-pa-lung-infection-and-suppression-of-th17%C3%A2-mediated-neutrophil-recruitment-in-exogenous-socs3-transfer-in-vitro
#7
Feng-Ming Ding, Ruo-Min Liao, Yu-Qing Chen, Guo-Gang Xie, Peng-Yu Zhang, Ping Shao, Min Zhang
Neutrophilic airway inflammation in chronic lung infections caused by Pseudomonas aeruginosa (PA) is associated with T helper (Th)17 responses. Suppressor of cytokine signaling 3 (SOCS3) is the major negative modulator of Th17 function through the suppression of signal transducer and activator of transcription (STAT)3 activation. The aim of the present study was to investigate the expression of SOCS3 in lung CD4+ T cells in a mouse model of chronic PA lung infection and the effect of exogenous SOCS3 on Th17‑mediated neutrophil recruitment in vitro...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28550122/the-blood-borne-sialyltransferase-st6gal-1-is-a-negative-systemic-regulator-of-granulopoiesis
#8
Christopher W L Dougher, Alexander Buffone, Michael J Nemeth, Mehrab Nasirikenari, Eric E Irons, Paul N Bogner, Joseph T Y Lau
Responding to systemic demands in producing and replenishing end-effector blood cells is predicated on the appropriate delivery and interpretation of extrinsic signals to the HSPCs. The data presented herein implicate the systemic, extracellular form of the glycosyltransferase ST6Gal-1 in the regulation of late-stage neutrophil development. ST6Gal-1 is typically a membrane-bound enzyme sequestered within the intracellular secretory apparatus, but an extracellular form is released into the blood from the liver...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28498478/demethylation-of-mir-495-inhibits-cell-proliferation-migration-and-promotes-apoptosis-by-targeting-stat-3-in-breast-cancer
#9
Yi Chen, Donglin Luo, Wuguo Tian, Zhirong Li, Xiaohua Zhang
In breast cancer (BC), silencing of miRNA genes due to miRNA gene promoter methylation are the important mechanisms directly contributing to tumorigenesis and tumor progression. miRNA-495 (miR-495) has been reported to be a tumor suppressor gene in various cancers, but its role and regulation in BC remains unclear. In the present study, the level of miR-495 was inversely correlated with the expression of STAT-3 in BC tissues and cell lines. miR-495 can directly target 3'-UTR of STAT-3 mRNA and thereby decrease the expression of STAT-3 in MCF-7 and HCC1973 cells by Targetscan and Dual-luciferase assay...
May 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28495965/pias3-is-necessary-for-dorso-ventral-patterning-and-visual-response-of-retinal-cones-but-is-not-required-for-rod-photoreceptor-differentiation
#10
Christie K Campla, Hannah Breit, Lijin Dong, Jessica D Gumerson, Jerome E Roger, Anand Swaroop
Protein inhibitor of activated Stat 3 (Pias3) is implicated in guiding specification of rod and cone photoreceptors through post-translational modification of key retinal transcription factors. To investigate its role during retinal development, we deleted exon 2-5 of the mouse Pias3 gene, which resulted in complete loss of the Pias3 protein. Pias3(-/-) mice did not show any overt phenotype, and retinal lamination appeared normal even at 18 months. We detected reduced photopic b-wave amplitude by electroretinography following green light stimulation of postnatal day (P)21 Pias3(-/-) retina, suggesting a compromised visual response of medium wavelength (M) cones...
June 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28490464/perioperative-cox-2-and-beta-adrenergic-blockade-improves-metastatic-biomarkers-in-breast-cancer-patients-in-a-phase-ii-randomized-trial
#11
Lee Shaashua, Maytal Shabat-Simon, Rita Haldar, Pini Matzner, Oded Zmora, Moshe Shabtai, Eran Sharon, Tanir Allweis, Iris Barshack, Lucile Hayman, Jesusa M G Arevalo, Jeffrey Ma, Maya Horowitz, Steve W Cole, Shamgar Ben-Eliyahu
<br /> <p>Translational studies suggest that excess perioperative release of catecholamines and prostaglandins may facilitate metastasis and reduce disease-free survival. This trial tested the combined perioperative blockade of these pathways in breast cancer patients.</p> <br />Experimental Design: <br /> <p>In a randomized placebo-controlled biomarker trial, 38 early-stage breast cancer patients received 11 days of perioperative treatment with a beta-adrenergic antagonist (propranolol) and a cyclooxygenase-2 (COX-2) inhibitor (etodolac), beginning five days before surgery...
May 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28483666/docosahexaenoic-acid-inhibits-il-6-expression-via-ppar%C3%AE-mediated-expression-of-catalase-in-cerulein-stimulated-pancreatic-acinar-cells
#12
Eun Ah Song, Joo Weon Lim, Hyeyoung Kim
Cerulein pancreatitis mirrors human acute pancreatitis. In pancreatic acinar cells exposed to cerulein, reactive oxygen species (ROS) mediate inflammatory signaling by Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3, and cytokine induction. Docosahexaenoic acid (DHA) acts as an agonist of peroxisome proliferator activated receptor γ (PPARγ), which mediates the expression of some antioxidant enzymes. We hypothesized that DHA may induce PPARγ-target catalase expression and reduce ROS levels, leading to the inhibition of JAK2/STAT3 activation and IL-6 expression in cerulein-stimulated acinar cells...
May 5, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28476239/defective-il-4-signaling-in-t-cells-defines-severe-common-variable-immunodeficiency
#13
Eli Taraldsrud, Børre Fevang, Silje F Jørgensen, Kristine Moltu, Vera Hilden, Kjetil Taskén, Pål Aukrust, June H Myklebust, Johanna Olweus
Common variable immunodeficiency (CVID) is defined by hypogammaglobulinemia and B-cell dysfunction, with significant clinical and immunological heterogeneity. Severe non-infectious complications, such as autoimmunity, granulomatous disease and splenomegaly, constitute a major cause of morbidity in CVID patients. T cells are generally regarded important for development of these clinical features. However, while T-cell abnormalities have been found in CVID patients, functional characteristics of T cells corresponding to well-defined clinical subtypes have not been identified...
July 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28463395/clinical-relevance-of-circulating-anti-ena-and-anti-dsdna-secreting-cells-from-sle-patients-and-their-dependence-on-stat-3-activation
#14
Raquel de la Varga Martínez, Beatriz Rodríguez-Bayona, Gustavo A Añez, Fermín Medina Varo, José J Pérez Venegas, José A Brieva, Carmen Rodríguez
Disturbances of plasma cell homeostasis and auto-antibody production are hallmarks of systemic lupus erythematosus. The aim of this study was to explore the presence of circulating anti-ENA and anti-dsDNA antibody-secreting cells, to determine their dependence on plasma cell-niche cytokines and to analyze their clinical value. The study was performed in SLE patients with serum anti-ENA and/or anti-dsDNA antibodies (n = 57). Enriched B-cell fractions and sorted antibody-secreting cells (CD19(low) CD38(high) ) were obtained from blood...
May 2, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28450947/the-inflammatory-cytokine-il-22-promotes-murine-gliomas-via-proliferation
#15
Xiguo Liu, Junjing Yang, Wankai Deng
Interleukin (IL)-22 is newly identified proinflammatory cytokine involved in the T helper (Th)17 and Th22 response. However, the possible role of IL-22 in glioma remains uncertain. The results of the present study demonstrated higher expression levels of IL-22 and the receptor IL-22BP in the brain of GL261 glioma-inoculation mice, suggesting the regulatory role of IL-22 in glioma. Injection of IL-22 increased the severity of glioma in vivo and higher expression levels of IL-6, IL-1β and tumor necrosis factor (TNF)-α were detected in the brain using ELISA following IL-22 injection...
March 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28442260/synthesis-of-benzoxazole-derivatives-as-interleukin-6-antagonists
#16
Darong Kim, Hee Yeon Won, Eun Sook Hwang, Young-Kook Kim, Hea-Young Park Choo
A growing number of studies have demonstrated that interleukin (IL)-6 plays pathological roles in the development of chronic inflammatory disease and autoimmune disease by activating innate immune cells and by stimulating adaptive inflammatory T cells. So, suppression of IL-6 function may be beneficial for prevention and treatment of chronic inflammatory disease. This study reports that a series of synthetic derivatives of benzoxazole have suppressive effects on IL-6-mediated signaling. Among 16 synthetic derivatives of benzoxazole, the compounds 4, 6, 11, 15, 17, and 19 showed a strong suppressive activity against IL-6-induced phosphorylation of signal transducer and activator of transcription (STAT) 3 by 80-90%...
April 7, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28441794/reciprocal-interactions-of-leukemic-cells-with-bone-marrow-stromal-cells-promote-enrichment-of-leukemic-stem-cell-compartments-in-response-to-curcumin-and-daunorubicin
#17
Saeed Mohammadi, Mohsen Nikbakht, Seyed Mehdi Sajjadi, Fariba Rad, Bahram Chahardouli, Javid Sabour Takanlu, Shahrbano Rostami, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
A predominant challenge in developing curative leukemia therapy is interactions of leukemic cells with the bone marrow stromal microenvironment. We aimed to investigate the role of stromal cells, such as bone marrow mesenchymal stromal cells (BMSCs) and osteoblasts (OBs), in curcumin (CUR) and daunorubicin (DNR) induced apoptosis of acute myeloid leukemia (AML) cells. We used KG1 and U937 as leukemia cell line models and treated them with CUR and DNR. The cells were then co-cultured with BMSCs or a combination of BMSCs and OBs as feeders...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28424262/magnesium-reduces-hepatic-lipid-accumulation-in-yellow-catfish-pelteobagrus-fulvidraco-and-modulates-lipogenesis-and-lipolysis-via-ppara-jak-stat-and-ampk-pathways-in-hepatocytes
#18
Chuan-Chuan Wei, Kun Wu, Yan Gao, Li-Han Zhang, Dan-Dan Li, Zhi Luo
Background: Magnesium influences hepatic lipid deposition in vertebrates, but the underlying mechanism is unknown.Objective: We used yellow catfish and their isolated hepatocytes to test the hypothesis that magnesium influences lipid deposition by modulating lipogenesis and lipolysis.Methods: Juvenile yellow catfish (mean ± SEM weight: 3.43 ± 0.02 g, 3 mo old, mixed sex) were fed a 0.14- (low), 0.87- (intermediate) or 2.11- (high) g Mg/kg diet for 56 d. Primary hepatocytes were incubated for 48 h in control or MgSO4-containing medium with or without 2-h pretreatment with an inhibitor (AG490, GW6471, or Compound C)...
April 19, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28420927/in-silico-analysis-of-fragile-histidine-triad-involved-in-regression-of-carcinoma
#19
Muhammad Asif Rasheed, Fatima Tariq, Sara Afzal, Shazia Mannanv
Hepatocellular carcinoma (HCCa) is a primary malignancy of the liver. Many different proteins are involved in HCCa including insulin growth factor (IGF) II , signal transducers and activators of transcription (STAT) 3, STAT4, mothers against decapentaplegic homolog 4 (SMAD 4), fragile histidine triad (FHIT) and selective internal radiation therapy (SIRT) etc. The present study is based on the bioinformatics analysis of FHIT protein in order to understand the proteomics aspect and improvement of the diagnosis of the disease based on the protein...
April 2017: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/28413603/hepatitis-b-virus-promotes-cancer-cell-migration-by-downregulating-mir-340-5p-expression-to-induce-stat3-overexpression
#20
Qiushuang Xiong, Shaoshuai Wu, Jingwen Wang, Xianhuang Zeng, Jianwen Chen, Mingcong Wei, Haotong Guan, Chengpeng Fan, Lang Chen, Deyin Guo, Guihong Sun
BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and infection with hepatitis B virus (HBV) is a leading cause of HCC. Previous studies have demonstrated that expression of the tumor inhibitor miR-340 is significantly downregulated in HCC tissues compared with normal liver tissues. However, the precise biological role of miR-340-5p in HBV-HCC and its molecular mechanism of action remain unknown. RESULTS: Expression of miR-340-5p was downregulated in HBV-associated HCC liver tissue and HBV-infected cells, facilitating migration of liver cancer cells...
2017: Cell & Bioscience
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