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https://www.readbyqxmd.com/read/29140265/anti-inflammatory-potential-of-1-nitro-2-phenylethylene
#1
Michelle A Sugimoto, Márcia de Jesus Amazonas da Silva, Larissa Froede Brito, Rosivaldo Dos Santos Borges, Flávio Almeida Amaral, Ana Paula de Araujo Boleti, Maritza Echevarria Ordoñez, Jose Carlos Tavares, Lirlandia Pires Sousa, Emerson Silva Lima
Inflammation is a reaction of the host to infectious or sterile stimuli and has the physiological purpose of restoring tissue homeostasis. However, uncontrolled or unresolved inflammation can lead to tissue damage, giving rise to a plethora of chronic inflammatory diseases, including metabolic syndrome and autoimmunity pathologies with eventual loss of organ function. Beta-nitrostyrene and its derivatives are known to have several biological activities, including anti-edema, vasorelaxant, antiplatelet, anti-inflammatory, and anticancer...
November 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29139546/up-regulation-of-pyk2-pkc%C3%AE-dependent-ho-1-by-co-releasing-molecule-corm-2-attenuates-tnf-%C3%AE-induced-lung-inflammation
#2
Chih-Chung Lin, Yu-Ching Chiang, Rou-Ling Cho, Wei-Ning Lin, Chien-Chung Yang, Li-Der Hsiao, Chuen-Mao Yang
BACKGROUND AND PURPOSE: Heme oxygenase-1 (HO-1) could provide cytoprotection against various inflammatory diseases. However, the mechanisms underlying carbon monoxide-releasing molecule-2 (CORM-2)-induced HO-1 expression protecting against TNF-α-induced inflammatory responses in human pulmonary alveolar epithelial cells (HPAEpiCs) remain unknown. EXPERIMENTAL APPROACH: CORM-2-induced HO-1 protein and mRNA expression, and signaling pathways were determined by Western blot and real-time PCR, coupled using respective pharmacological inhibitors or transfection with siRNAs...
November 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29138986/secukinumab-in-active-rheumatoid-arthritis-after-anti-tnf%C3%AE-therapy-a-randomized-double-blind-placebo-controlled-phase-3-study
#3
Hasan Tahir, Atul Deodhar, Mark Genovese, Tsutomu Takeuchi, Jacob Aelion, Filip Van den Bosch, Sibylle Haemmerle, Hanno B Richards
INTRODUCTION: 'REASSURE' (NCT01377012), a phase 3 study, evaluated the efficacy and safety of secukinumab in patients with active rheumatoid arthritis (RA) who had an inadequate response to, or intolerance of, tumor necrosis factor inhibitors (TNF-inhibitors). METHODS: A total of 637 patients were randomized (1:1:1) to receive intravenous secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous secukinumab 150 mg or 75 mg every 4 weeks (starting from week 8) or placebo at the same dosing schedule...
November 14, 2017: Rheumatology and Therapy
https://www.readbyqxmd.com/read/29138863/therapeutic-effect-of-ulinastatin-on-pulmonary-fibrosis-via-downregulation-of-tgf%C3%A2-%C3%AE-1-tnf%C3%A2-%C3%AE-and-nf%C3%A2-%C3%AE%C2%BAb
#4
Dejun Li, Hongsheng Ji, Bao Zhao, Chunyang Xu, Wenjun Xia, Lihui Han, Dongqing Yu, Yuanrong Ju, Changjun Jin
Pulmonary fibrosis is a chronic, progressive, lethal lung disease characterized by alveolar cell necrosis and dysplasia of interstitial fibrotic tissue, resulting in loss of lung function and eventual respiratory failure. Previously, glucocorticoid drugs were used to treat this lung disorder. However, positive responses were recorded in less than half of treated patients and the cytotoxicity caused by high dosage treatment is still a concern. The present study investigated whether ulinastatin, a typical urinary trypsin inhibitor that mitigates numerous inflammatory responses, could be a treatment option for lung fibrosis...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138810/angiotensin-converting-enzyme-2-angiotensin-1-7-mas-axis-prevents-pancreatic-acinar-cell-inflammatory-response-via-inhibition-of-the-p38-mitogen-activated-protein-kinase-nuclear-factor-%C3%AE%C2%BAb-pathway
#5
Xiaozheng Yu, Lijian Cui, Fei Hou, Xiaoya Liu, Yan Wang, Yan Wen, Cheng Chi, Chunyun Li, Ruixia Liu, Chenghong Yin
The aim of the present study was to investigate the role of the angiotensin-converting enzyme (ACE)2-angiotensin‑(Ang)-(1-7)-Mas axis in the pathogenesis of pancreatitis and the association between this axis and the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor (NF-κB) signaling pathway in pancreatic acinar cells. Mouse pancreatic acinar cancer (MPC-83) cells were stimulated with 10 nM caerulein (CAE) to create an in vitro model of acute pancreatitis, and collected for analysis at 2, 6, 12, 24 and 48 h post stimulation...
November 13, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29136772/trimethylamine-n-oxide-promotes-atherosclerosis-via-cd36-dependent-mapk-jnk-pathway
#6
Jin Geng, Chenchen Yang, Bingjian Wang, Xiwen Zhang, Tingting Hu, Yang Gu, Ju Li
BACKGROUND: Many studies have identified trimethylamine N-oxide (TMAO) as a new risk factor of cardiovascular diseases. It has been suggested that TMAO promotes atherosclerosis development. However, the underlying mechanism is still unclear. METHODS: Apoe-/- mice were fed a high-fat diet and given water with or without TMAO for 8-week. Histological and immunohistological analyses were used to evaluate the atherogenic effect of TMAO in vivo. We also employed peritoneal elicited macrophages and RAW264...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29134442/endothelial-tnf-%C3%AE-induction-by-hsp60-secreted-from-thp-1-monocytes-exposed-to-hyperglycaemic-conditions
#7
Ryan Dennis Martinus, Julie Goldsbury
A non-resolving inflammation of the endothelium is recognised to be an important process leading to atherosclerosis. In diabetes, this process is thought to account for a significant number of cardiovascular disease-associated death and disability. However, the molecular mechanisms by which diabetes contributes to endothelial inflammation remain to be established. Whilst there is some evidence linking hyperglycaemia-induced reactive oxygen species (ROS) formation by the mitochondrial electron-transport chain to oxidative stress, cellular injury and apoptosis in the endothelium, a clear link to endothelium inflammation has not yet been established...
November 13, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/29131527/3d-matrix-embedding-inhibits-cycloheximide-mediated-sensitization-to-tnf-alpha-induced-apoptosis-of-human-endothelial-cells
#8
Michael Saemisch, Markus Nickmann, Lisa Riesinger, Elazer R Edelman, Heiko Methe
The programmed form of cell death (apoptosis) is essential for normal development of multicellular organisms. Dysregulation of apoptosis has been linked with embryonal death and is involved in the pathophysiology of various diseases. Others and we previously demonstrated endothelial biology being intertwined with biochemical and structural composition of the subendothelial basement membrane. We now demonstrate that a three-dimensional growing environment significantly shields endothelial cells from cytokine-induced apoptosis...
November 13, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29131242/synergistic-effects-of-chlorambucil-and-trail-on-apoptosis-and-proliferation-of-raji-cells
#9
J-X Guo, Y-H Zhou, Y-Q Huang, G-J Liu, J-X Pan
OBJECTIVE: Tumor necrosis factor (TNF) related apoptosis inducing ligand (TRAIL) can induce the apoptosis of tumor cells, but leaving its effect on malignant lymphoma largely insignificant, as these tumors may develop drug resistance. Chlorambucil (CLB) had definitive treatment efficacy on low-malignant non-Hodgkin lymphoma (NHL), but with unclear efficacy on highly malignant Burkitt lymphoma. A study has been shown that CLB could enhance the sensitivity of chronic lymphatic leukemia cells against TRAIL...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29131009/effects-of-microrna-499-on-the-inflammatory-damage-of-endothelial-cells-during-coronary-artery-disease-via-the-targeting-of-pdcd4-through-the-nf-%C3%AE-%C3%AE-tnf-%C3%AE-signaling-pathway
#10
Yu-Hong Zhang, Keng He, Gang Shi
BACKGROUND/AIMS: This study aimed to analyze the impact of microRNA-499 (miR-499) on the inflammatory damage of endothelial cells during coronary artery disease (CAD) via the targeting of PDCD4 through the NF-kB/ TNF-α signaling pathway. METHODS: A total of 216 CAD patients (CAD group) and 90 healthy people (normal group) were enrolled in our study. Endothelial cells were collected and assigned into normal, OX-LDL, negative control (NC), miR-499 inhibitor, miR-499 mimic, PDCD4 siRNA, and miR-499 inhibitor + PDCD4 siRNA groups...
November 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29130929/tnf-regulates-transcription-of-nlrp3-inflammasome-components-and-inflammatory-molecules-in-cryopyrinopathies
#11
Matthew D McGeough, Alexander Wree, Maria E Inzaugarat, Ariela Haimovich, Casey D Johnson, Carla A Peña, Raphaela Goldbach-Mansky, Lori Broderick, Ariel E Feldstein, Hal M Hoffman
The NLRP3 inflammasome is a protein complex responsible for caspase-1-dependent maturation of the proinflammatory cytokines IL-1β and IL-18. Gain-of-function missense mutations in NLRP3 cause the disease spectrum known as the cryopyrin-associated periodic syndromes (CAPS). In this study, we generated Nlrp3-knockin mice on various KO backgrounds including Il1b/Il18-, caspase-1-, caspase-11- (Casp1/11-), and Tnf-deficient strains. The Nlrp3L351P Il1b-/- Il18-/- mutant mice survived and grew normally until adulthood and, at 6 months of age, exhibited marked splenomegaly and leukophilia...
November 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29129493/overexpression-of-microrna-495-improves-the-intestinal-mucosal-barrier-function-by-targeting-stat3-via-inhibition-of-the-jak-stat3-signaling-pathway-in-a-mouse-model-of-ulcerative-colitis
#12
Xian-Qun Chu, Jing Wang, Guang-Xiang Chen, Guan-Qi Zhang, De-Yong Zhang, Yong-Yan Cai
We aim to investigate the role of microRNA-495 (miR-495) in the intestinal mucosal barrier by indirectly targeting signal transducer and activator of transcription 3 (STAT3) through the Janus kinase-signal transducer and activator of transcription (JAK)/STAT3 signaling pathway in a mouse model of ulcerative colitis (UC). BALB/c mice were selected for establishing mice model of UC, and intestinal tissues of normal and UC mice were collected. ELISA was conducted for detecting levels of TNF-α, IL-6, IFN-γ and IL-10...
October 12, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29128927/toll-like-receptors-participate-in-naegleria-fowleri-recognition
#13
Moisés Martínez-Castillo, Leopoldo Santos-Argumedo, José Manuel Galván-Moroyoqui, Jesús Serrano-Luna, Mineko Shibayama
Naegleria fowleri is a protozoan that invades the central nervous system and causes primary amoebic meningoencephalitis. It has been reported that N. fowleri induces an important inflammatory response during the infection. In the present study, we evaluated the roles of Toll-like receptors in the recognition of N. fowleri trophozoites by human mucoepithelial cells, analyzing the expression and production of innate immune response mediators. After amoebic interactions with NCI-H292 cells, the expression and production levels of IL-8, TNF-α, IL-1β, and human beta defensin-2 were evaluated by RT-PCR, ELISA, immunofluorescence, and dot blot assays, respectively...
November 11, 2017: Parasitology Research
https://www.readbyqxmd.com/read/29128706/consumption-of-ellagic-acid-and-dihydromyricetin-synergistically-protects-against-uv-b-induced-photoaging-possibly-by-activating-both-tgf-%C3%AE-1-and-wnt-signaling-pathways
#14
Na Rang Moon, Suna Kang, Sunmin Park
Ellagic acid (EGA) and dihydromyricetin (DHM) are both found in fruits and vegetables are used for anti-aging treatment for the skin. The anti-photoaging efficacy of EGA and DHM was investigated in UV-B irradiated skin in vivo and the involvement of transforming growth factor (TGF)-β1 and wnt signaling pathways were examined in vitro. HaCaT cells were treated with either 50μM EGA, 50μM DHM or 25μM EGA+25μM DHM before 100mJ/cm(2) UV-B exposure, and then oxidative stress and inflammation was measured. The involvement of TGF-β1 and wnt signaling was measured using their inhibitors, respectively, in HaCaT cells...
November 7, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29128090/crocus-sativus-l-aqueous-extract-reduces-atherogenesis-increases-atherosclerotic-plaque-stability-and-improves-glucose-control-in-diabetic-atherosclerotic-animals
#15
Ei Christodoulou, N P E Kadoglou, M Stasinopoulou, O A Konstandi, C Kenoutis, Z I Kakazanis, A Rizakou, N Kostomitsopoulos, G Valsami
BACKGROUND AND AIMS: We aimed to evaluate a possible atheroprotective effect of saffron aqueous extract (SFE), and its potential anti-inflammatory mechanisms, in apoE knockout (ApoE(-/-)) mice. METHODS: Fifty male, ApoE(-/-) mice, fed a high-fat diet (HFD) for 12 weeks, were randomized into 5 groups: (1) baseline group, euthanatized, without intervention, (2) three saffron groups, receiving HFD and 30,60,90 mg/kg/day of SFE, respectively, for four weeks, per os through gavage, after reconstitution in water for injection (WFI), (3) control group (COG), receiving daily HFD and the same volume of WFI (four weeks)...
November 1, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29127443/astragaloside-iv-attenuates-orbital-inflammation-in-graves-orbitopathy-through-suppression-of-autophagy
#16
Hong Li, Yali Zhang, Jie Min, Long Gao, Ren Zhang, Yucheng Yang
INTRODUCTION: Graves' orbitopathy (GO) is an autoimmune inflammatory disorder affecting the orbit around the eye. Astragaloside IV (AS-VI) is the main active ingredient of the Chinese herbal medicine Huangqi (Radix Astragali Mongolici). AS-IV exhibits antioxidant and anti-inflammatory properties, and shows therapeutic potential in a number of ischemic and inflammatory diseases; however, its pharmaceutical activities in GO remain undefined. MATERIALS AND METHODS: In this study, we investigated the effects of AS-IV on interleukin (IL)-1β-induced orbital fibroblast inflammation in vitro and GO orbital inflammation and ocular histopathological changes in vivo, as well as the underlying mechanisms responsible for these effects...
November 10, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29127109/incb040093-is-a-novel-pi3k%C3%AE-inhibitor-for-the-treatment-of-b-cell-lymphoid-malignancies
#17
Niu Shin, Yun-Long Li, Song Mei, Kathy He Wang, Leslie Hall, Kamna Katiyar, Qian Wang, Gengjie Yang, Beth Rumberger, Lynn Leffet, Xin He, Mark Rupar, Kevin Bowman, Margaret Favata, Jun Li, Mike Liu, Yanlong Li, Maryanne Covington, Holly Koblish, Maxim Soloviev, Dana Shuey, Timothy Burn, Sharon Diamond, Jordan Fridman, Andrew Combs, Wenqing Yao, Swamy Yeleswaram, Gregory Hollis, Kris Vaddi, Reid Huber, Robert Newton, Peggy Scherle
PI3Kδ is a critical signaling molecule in B cells and is considered a target for development of therapies against various B cell malignancies. INCB040093 is a novel PI3Kδ small molecule inhibitor and has demonstrated promising efficacy in patients with Hodgkin's lymphoma in clinical studies. Here, we disclose the chemical structure and the preclinical activity of the compound. In biochemical assays, INCB040093 potently inhibits the PI3Kδ kinase, with 74 to >900-fold selectivity against other PI3K family members...
November 10, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29125891/profiling-response-to-tnf-inhibitor-treatment-in-axial-spondyloarthritis
#18
Mansour Alazmi, Ismail Sari, Bharath Krishnan, Robert D Inman, Nigil Haroon
OBJECTIVES: Lack of response to TNF inhibitory (TNFi) agents is not uncommon, encountered during the treatment of axial spondyloarthritis (AxSpA) patients and can be classified as primary (PLR) or secondary (SLR) lack of response. The primary aim of this study was to evaluate factors associated with TNFi failure types and their characteristics in AxSpA. METHODS: Adult AxSpA patients who were TNFi naive at the time of baseline evaluation and started on their first biologics for active axial disease were identified...
November 10, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/29123181/carnosol-controls-the-human-glioblastoma-stemness-features-through-the-epithelial-mesenchymal-transition-modulation-and-the-induction-of-cancer-stem-cell-apoptosis
#19
Chiara Giacomelli, Simona Daniele, Letizia Natali, Caterina Iofrida, Guido Flamini, Alessandra Braca, M Letizia Trincavelli, Claudia Martini
A high cell proliferation rate, invasiveness and resistance to chemotherapy are the main features of glioblastoma (GBM). GBM aggressiveness has been widely associated both with a minor population of cells presenting stem-like properties (cancer stem-like cells, CSCs) and with the ability of tumor cells to acquire a mesenchymal phenotype (epithelial-mesenchymal transition, EMT). Carnosol (CAR), a natural inhibitor of MDM2/p53 complex, has been attracted attention for its anti-cancer effects on several tumor types, including GBM...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29122888/tnf-stimulated-gene-6-promotes-formation-of-hyaluronan-inter-%C3%AE-inhibitor-heavy-chain-complexes-necessary-for-ozone-induced-airway-hyperresponsiveness
#20
Vandy P Stober, Collin G Johnson, Alana Majors, Mark E Lauer, Valbona Cali, Ronald J Midura, Hans-Georg Wisniewski, Mark A Aronica, Stavros Garantziotis
Exposure to pollutants, such as ozone, exacerbates airway inflammation and hyperresponsiveness (AHR). TNF-stimulated gene 6 (TSG-6) is required to transfer inter-α-inhibitor heavy chains (HC) to hyaluronan (HA), facilitating HA receptors binding. TSG-6 is necessary for AHR in allergic asthma, because it facilitates the development of a pathological HA-HC matrix. However, the role of TSG-6 in acute airway inflammation is not well understood. Here, we hypothesized that TSG-6 is essential for the development of HA- and ozone-induced AHR...
November 9, 2017: Journal of Biological Chemistry
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