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https://www.readbyqxmd.com/read/29332916/mir-135a-promotes-inflammatory-responses-of-vascular-smooth-muscle-cells-from-db-db-mice-via-downregulation-of-foxo1
#1
Xiaochun Lu, Dawei Yin, Bo Zhou, Tieling Li
It has been shown that microRNAs (miRNAs) greatly affect the functions of vascular smooth muscle cells (VSMC), but the effects of mRNAs under diabetic conditions remain unclear.Using a model of diabetic db/db mice, we studied the functions of microRNA-135a (miR-135a) during VSMC dysfunction.Compared to control WT mice, miR-135a expression in VSMC was significantly increased while the level of forkhead box O1 (FOXO1) protein decreased significantly. After transfecting miR-135a mimics into VSMC, the expression of FOXO1 was decreased, while cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein-1 (MCP-1) expression levels were increased, thus promoting the interaction between monocytes and WT VSMC...
January 15, 2018: International Heart Journal
https://www.readbyqxmd.com/read/29329697/ageing-perceptions-and-non-adherence-to-aromatase-inhibitors-among-breast-cancer-survivors
#2
Moriah J Brier, Dianne L Chambless, Jinbo Chen, Jun J Mao
PURPOSE: Aromatase inhibitors (AIs) are a potentially life-saving treatment for breast cancer survivors, yet poor adherence to treatment is a prevalent problem. A common adverse effect of AI treatment is arthralgia, which is identified by survivors as a major reason for treatment discontinuation. Women who experience arthralgia on AIs often report feeling they have aged rapidly while on the treatment. In the present study, we examined whether arthralgia-associated ageing perceptions predicted non-adherence...
January 9, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29328551/failure-of-monotherapy-in-clinical-practice-in-patients-with-type-2-diabetes-the-korea-national-diabetes-program
#3
Ja Young Jeon, Soo Jin Lee, Sieun Lee, Soo Jin Kim, Seung Jin Han, Hae Jin Kim, Dae Jung Kim, Young Seol Kim, Jeong Taek Woo, Kyu Jeung Ahn, Moonsuk Nam, Sei Hyun Baik, Yongsoo Park, Kwan-Woo Lee
AIMS: We investigated the failure of monotherapy in patients with type 2 DM in real practice settings. METHODS: The Korea National Diabetes Program was a prospective, multicenter observational cohort study of type 2 DM patients in Korea. Of the 3,950 patients enrolled in the study, we studied 998 who were continuously maintained on monotherapy for at least 90 days at six participating centers. To balance the baseline characteristics of patients in each group, we employed propensity-matching at a 1:1 ratio (metformin vs...
January 12, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29326169/dual-cyclooxygenase-fatty-acid-amide-hydrolase-inhibitor-exploits-novel-binding-interactions-in-the-cyclooxygenase-active-site
#4
Michael C Goodman, Shu Xu, Carol A Rouzer, Surajit Banerjee, Kebreab Ghebreselasie, Marco Migliore, Daniele Piomelli, Lawrence J Marnett
The cyclooxygenases COX-1 and COX-2 oxygenate arachidonic acid (AA) to prostaglandin H2 (PGH2). COX-2 also oxygenates the endocannabinoids, 2-arachidonoylglycerol (2-AG) and arachidonoylethanolamide (AEA), to the corresponding PGH2 analogs. Both enzymes are targets of nonsteroidal anti-inflammatory drugs (NSAIDs), but NSAID-mediated COX inhibition is associated with gastrointestinal toxicity. One potential strategy to counter this toxicity is to also inhibit fatty acid amide hydrolase (FAAH), which hydrolyzes bioactive fatty acid ethanolamides (FAEs) into fatty acids and ethanolamine...
January 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29323698/xist-accelerates-neuropathic-pain-progression-through-regulation-of-mir-150-and-zeb1-in-cci-rat-models
#5
Xue-Tao Yan, Jing-Min Lu, Yu Wang, Xiao-Li Cheng, Xiang-Hu He, Wen-Zhong Zheng, Hu Chen, Yan-Lin Wang
LncRNAs are reported to participate in neuropathic pain development. LncRNA X-inactive specific transcript (XIST) is involved in the progression of various cancers. However, the role of XIST in neuropathic pain remains unclear. In our present study, we established a chronic constriction injury (CCI) rat model and XIST was found to be greatly upregulated both in the spinal cord tissues and in the isolated microglias of CCI rats. Inhibition of XIST inhibited neuropathic pain behaviors including mechanical and thermal hyperalgesia...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29321644/cox-2-induces-oncogenic-micro-rna-mir655-in-human-breast-cancer
#6
Mousumi Majumder, Leanna Dunn, Ling Liu, Asma Hasan, Krista Vincent, Muriel Brackstone, David Hess, Peeyush K Lala
We show that Cyclooxygenase-2 over-expression induces an oncogenic microRNA miR655 in human breast cancer cells by activation of EP4. MiR655 expression positively correlated with COX-2 in genetically disparate breast cancer cell lines and increased in all cell lines when grown as spheroids, implicating its link with stem-like cells (SLCs). Ectopic miR655 over-expression in MCF7 and SKBR3 cells resulted in increased proliferation, migration, invasion, spheroid formation and Epithelial to Masenchymal transition (EMT)...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321620/lack-of-pink1-alters-glia-innate-immune-responses-and-enhances-inflammation-induced-nitric-oxide-mediated-neuron-death
#7
Liuke Sun, Ruifang Shen, Sandeep K Agnihotri, Yun Chen, Zhiwei Huang, Hansruedi Büeler
Neuroinflammation is involved in the pathogenesis of Parkinson's disease (PD) and other neurodegenerative disorders. We show that lack of PINK1- a mitochondrial kinase linked to recessive familial PD - leads to glia type-specific abnormalities of innate immunity. PINK1 loss enhances LPS/IFN-γ stimulated pro-inflammatory phenotypes of mixed astrocytes/microglia (increased iNOS, nitric oxide and COX-2, reduced IL-10) and pure astrocytes (increased iNOS, nitric oxide, TNF-α and IL-1β), while attenuating expression of both pro-inflammatory (TNF-α, IL-1β) and anti-inflammatory (IL-10) cytokines in microglia...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29318300/design-synthesis-and-anti-inflammatory-activity-of-derivatives-10-r-3-aryl-6-7-dihydro-2h-1-2-4-triazino-2-3-c-quinazolin-2-ones-of-spiro-fused-cyclic-frameworks
#8
Oleksandra Kolomoets, Оleksii Voskoboynik, Oleksii Antypenko, Galyna Berest, Inna Nosulenko, Vitaliy Palchikov, Olexandr Karpenko, Sergiy Kovalenko
Present work is devoted to the purposeful search of novel promising anti-inflammatory agents among the insufficiently known 3'-R-10'-R1-spiro[hetaryl-3(4),6'-[1,2,4]triazino[2,3-c]quinazolin]-2'(7'H)-ones. The virtual combinatorial library of previously unknown spiro-condensed derivatives of [1,2,4]triazino[2,3-c]quinazolines was formed and promising COX-2 inhibitors were identified by molecular docking method. Potential anti-inflammatory agents were synthesized by [5+1]-cyclocondensation of substituted 3-(2-aminophenyl)-6-R-1,2,4-triazin-5(2H)-ones with heterocyclic ketones...
December 2017: Acta Chimica Slovenica
https://www.readbyqxmd.com/read/29317963/neutrophil-to-lymphocyte-ratio-predicts-overall-survival-of-advanced-non-small-cell-lung-cancer-harboring-mutant-epidermal-growth-factor-receptor
#9
Seigo Minami, Yoshitaka Ogata, Shouichi Ihara, Suguru Yamamoto, Kiyoshi Komuta
Background: Neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) have been demonstrated to be prognostic biomarkers in various cancers, including non-small cell lung cancer (NSCLC). However, little has been known about these two ratios for a specific population of NSCLC harboring active epidermal growth factor receptor (EGFR) mutation. Methods: We retrospectively reviewed electrical medical records of 152 patients who met the following criteria: NSCLC harboring mutant EGFR, EGFR-tyrosine kinase inhibitor (EGFR-TKI) monotherapy initiated between October 2007 and February 2017 at our hospital, stage III-IV or post-surgical recurrence...
December 2017: World Journal of Oncology
https://www.readbyqxmd.com/read/29310667/wwl70-protects-against-chronic-constriction-injury-induced-neuropathic-pain-in-mice-by-cannabinoid-receptor-independent-mechanisms
#10
Jie Wen, Melissa Jones, Mikiei Tanaka, Prabhuanand Selvaraj, Aviva J Symes, Brian Cox, Yumin Zhang
BACKGROUND: Targeting the endocannabinoid system has emerged as an effective strategy for the treatment of inflammatory and neurological diseases. Unlike the inhibition of the principal 2-arachidonyl glycerol (2-AG) hydrolytic enzyme monoacylglycerol lipase (MAGL), which leads to 2-AG overload and cannabinoid receptor desensitization, selective inhibition of the minor 2-AG hydrolytic enzyme alpha, beta-hydrolase domain 6 (ABHD6) can provide therapeutic benefits without producing cannabimimetic side effects...
January 8, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29306822/celecoxib-a-cyclooxygenase-2-inhibitor-offers-chemoprevention-against-reproductive-and-neurobehavioural-abnormalities-induced-by-atrazine-in-male-wistar-rats
#11
O E Kale, T O Oyesola, F S Raji
The cyclooxygenase-2/prostanoid pathway (COX-2) serves as a potential therapeutic target in various pathological conditions. Thus, the modulatory effect of celecoxib (CXB), a COX-2 inhibitor, in atrazine-induced toxicity was investigated. Five groups (n = 6 rats per group) of adult male Wistar rats received corn oil (2 ml/kg), atrazine (ATZ, 300 mg/kg) and CXB (5.7 mg/kg) respectively and their combinations via the oral route. Results obtained showed reduced (p < 0.05) sperm motility (25.8%) and counts (27...
December 30, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29306052/celecoxib-prevents-cognitive-impairment-and-neuroinflammation-in-soluble-amyloid-%C3%AE-treated-rats
#12
Emanuela Mhillaj, Maria Grazia Morgese, Paolo Tucci, Anna Furiano, Livio Luongo, Maria Bove, Sabatino Maione, Vincenzo Cuomo, Stefania Schiavone, Luigia Trabace
Recent findings suggest that soluble forms of amyloid-β (sAß) peptide contribute to synaptic and cognitive dysfunctions in early stages of Alzheimer's disease (AD). On the other hand, neuroinflammation and cyclooxygenase-2 (COX-2) enzyme have gained increased interest as key factors involved early in AD, although the signaling pathways and pathophysiologic mechanisms underlying a link between sAß-induced neurotoxicity and inflammation are still unclear. Here, we investigated the effects of selective COX-2 enzyme inhibition on neuropathological alterations induced by sAβ administration in rats...
January 3, 2018: Neuroscience
https://www.readbyqxmd.com/read/29304843/effect-of-cox-2-inhibition-on-tendon-to-bone-healing-and-pge2-concentration-after-anterior-cruciate-ligament-reconstruction
#13
Martin Sauerschnig, Josef Stolberg-Stolberg, Carmen Schmidt, Valerie Wienerroither, Michael Plecko, Karin Schlichting, Carsten Perka, Christian Dynybil
BACKGROUND: Non-steroidal anti-inflammatory drugs are commonly used to reduce pain and inflammation in orthopaedic patients. Selective cyclooxygenase-2 (COX-2) inhibitors have been developed to minimize drug-specific side effects. However, they are suspected to impair both bone and tendon healing. The objective of this study is to evaluate the effect of COX-2 inhibitor administration on tendon-to-bone healing and prostaglandin E (PGE2) concentration. METHODS: Thirty-two New Zealand white rabbits underwent reconstructions of the anterior cruciate ligaments and were randomized into four groups: Two groups postoperatively received a selective COX-2 inhibitor (Celecoxib) on a daily basis for 3 weeks, the two other groups received no postoperative COX-2 inhibitors at all and were examined after three or 6 weeks...
January 5, 2018: European Journal of Medical Research
https://www.readbyqxmd.com/read/29302934/a-class-comparison-of-medication-persistence-in-people-with-type-2-diabetes-a-retrospective-observational-study
#14
Andrew McGovern, William Hinton, Silvio Calderara, Neil Munro, Martin Whyte, Simon de Lusignan
INTRODUCTION: Longer medication persistence in type 2 diabetes (T2D) is associated with improved glycaemic control. It is not clear which oral therapies have the best persistence. The objective of this study was to compare medication persistence across different oral therapies in people with T2D. METHODS: We performed a retrospective cohort analysis using a primary-care-based population, the Royal College of General Practitioners Research and Surveillance Centre cohort...
January 4, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29299942/docking-assisted-design-of-novel-4-adamantanyl-2-thiazolylimino-5-arylidene-4-thiazolidinones-as-potent-nsaids
#15
O Kouatly, Ph Eleftheriou, A Petrou, D Hadjipavlou-Litina, A Geronikaki
Docking analysis was used to predict the effectiveness of adamantanyl insertion in improving cycloxygenase/lipoxygenase (COX/LOX) inhibitory action of previously tested 2-thiazolylimino-5-arylidene-4-thiazolidinones. The crystal structure data of human 5-LOX (3O8Y), ovine COX-1 (1EQH) and mouse COX-2 (3ln1) were used for docking analysis. All docking calculations were carried out using AutoDock 4.2 software. Following prediction results, 11 adamantanyl derivatives were synthesized and evaluated for biological action...
January 4, 2018: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/29298131/a-systematic-review-of-p53-regulation-of-oxidative-stress-in-skeletal-muscle
#16
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
January 3, 2018: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29296784/high-proportions-of-pd-1-and-pd-l1-leukocytes-in-classical-hodgkin-lymphoma-microenvironment-are-associated-with-inferior-outcome
#17
Peter Hollander, Peter Kamper, Karin Ekstrom Smedby, Gunilla Enblad, Maja Ludvigsen, Julie Mortensen, Rose-Marie Amini, Stephen Hamilton-Dutoit, Francesco d'Amore, Daniel Molin, Ingrid Glimelius
Immune checkpoint inhibition targeting the programmed death receptor (PD)-1 pathway is a novel treatment approach in relapsed and refractory classical Hodgkin lymphoma (cHL). Identifying patients with a high risk of treatment failure could support the use of PD-1 inhibitors as front-line treatment. Our aim was to investigate the prognostic impact of PD-1, programmed death-ligand 1 (PD-L1), and PD-L2 in the tumor microenvironment in diagnostic biopsies of patients with cHL. Patients from Denmark and Sweden, diagnosed between 1990 and 2007 and ages 15 to 86 years, were included...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290997/targeting-g-protein-coupled-receptor-related-signaling-pathway-in-a-murine-xenograft-model-of-appendiceal-pseudomyxoma-peritonei
#18
Ashok K Dilly, Brendon D Honick, Yong J Lee, Zong S Guo, Herbert J Zeh, David L Bartlett, Haroon A Choudry
Cancer cells aberrantly express mucins to enhance their survival. Relative chemoresistance of appendiceal pseudomyxoma peritonei (PMP) is attributed to abundant extracellular mucin 2 (MUC2) protein production. We hypothesized that simultaneous MUC2 inhibition and apoptosis induction would be effective against mucinous tumors. In vitro studies were conducted using LS174T cells (MUC2-secreting human colorectal cancer cells), PMP explant tissue, and epithelial organoid cultures (colonoids) derived from mucinous appendix cancers...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285125/anti-inflammatory-effects-of-daehwangmokdantang-a-traditional-herbal-formulation-in-lipopolysaccharide-stimulated-raw-264-7-macrophages
#19
Moon Hee Lee, Su Hyun Hong, Cheol Park, Min-Ho Han, Sung Ok Kim, Sang Hoon Hong, Gi-Young Kim, Yung Hyun Choi
Daehwangmokdantang (DHMDT) is a traditional polyherbal formulation that has known antidiarrheal and anti-inflammatory activities. However, the underlying mechanisms of these activities are poorly understood. In the present study, the inhibitory effects of DHMDT on the production of proinflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages were investigated. The inhibitory effects of DHMDT on LPS-induced nitric oxide (NO), prostaglandin (PG)E2, tumor necrosis factor (TNF)-α and interleukin (IL)-1β production were examined using Griess reagent and ELISA detection kits...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29284644/cox-2-seh-dual-inhibitor-ptupb-potentiates-the-anti-tumor-efficacy-of-cisplatin
#20
Fuli Wang, Hongyong Zhang, Ai-Hong Ma, Weimin Yu, Maike Zimmermann, Jun Yang, Sung Hee Hwang, Daniel Zhu, Tzu-Yin Lin, Michael Malfatti, Kenneth W Turteltaub, Paul T Henderson, Susan Airhart, Bruce D Hammock, Jianlin Yuan, Ralph W de Vere White, Chong-Xian Pan
Cisplatin-based therapy is highly toxic, but moderately effective in most cancers. Concurrent inhibition of cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) results in anti-tumor activity, and has organ protective effects. The goal of this study was to determine the anti-tumor activity of PTUPB, an orally bioavailable COX-2/sEH dual inhibitor, in combination with cisplatin and gemcitabine (GC) therapy. NSG mice bearing bladder cancer patient-derived xenografts were treated with vehicle, PTUPB, cisplatin, GC or combinations thereof...
December 28, 2017: Molecular Cancer Therapeutics
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