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https://www.readbyqxmd.com/read/30121964/insights-from-multidimensional-analyses-of-the-pan-cancer-dna-methylome-heterogeneity-and-the-uncanonical-cpg-gene-associations
#1
Yang Liu, Rongyao Huang, Yu Liu, Wanlu Song, Yuting Wang, Yang Yang, Shengcheng Dong, Xuerui Yang
Although the DNA methylome profiles have been available in large cancer cohorts such as The Cancer Genome Atlas (TCGA), integrative analysis of the DNA methylome architectures in a pan-cancer manner is still limited. In the present study, we aimed to systematically dissect the insightful features related to the inter-tumoral DNA methylome heterogeneity in a pan-cancer context of 21 cancers in TCGA. First, pan-cancer clustering of the DNA methylomes revealed convergence of cancers and, meanwhile, new classifications of cancer subtypes, which are often associated to prognostic differences...
August 19, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/30121947/nampt-signaling-is-critical-for-the-proangiogenic-activity-of-tumor-associated-neutrophils
#2
Ekaterina Pylaeva, Mozhgan Dehghan Harati, Ilona Spyra, Sharareh Bordbari, Sarah Strachan, Basant Kumar Thakur, Benedikt Höing, Cindy Franklin, Julia Skokowa, Karl Welte, Dirk Schadendorf, Agnes Bankfalvi, Sven Brandau, Stephan Lang, Jadwiga Jablonska
Tumor-associated neutrophils regulate many processes associated with tumor progression, and depending on the microenvironment, they can exhibit pro- or antitumor functions. However, the molecular mechanisms regulating their tumorigenicity are not clear. Using transplantable tumor models, we showed here that Nicotinamide Phosphoribosyltransferase (NAMPT), a molecule involved in CSF3R downstream signaling, is essential for tumorigenic conversion of tumor-associated neutrophils and their pro-angiogenic switch...
August 19, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/30121899/fusobacterium-nucleatum-promotes-m2-polarization-of-macrophages-in-the-microenvironment-of-colorectal-tumours-via-a-tlr4-dependent-mechanism
#3
Ting Chen, Qing Li, Jiao Wu, Yaxin Wu, Wei Peng, Huan Li, Jianmei Wang, Xiaowei Tang, Yan Peng, Xiangsheng Fu
Fusobacterium nucleatum (Fn) has been shown to promote colorectal cancer (CRC) development by inhibiting host anti-tumour immunity. However, the impact of Fn infection on macrophage polarization and subsequent intestinal tumour formation as well as the underlying molecular pathways has not been investigated. We investigated the impact of Fn infection on macrophage polarization in human CRCs and cultured macrophages as well as the effects on macrophage phenotype and intestinal tumour formation in ApcMin/+ mice...
August 18, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/30121884/association-between-gstp1-ile105val-genetic-polymorphism-and-dependency-to-heroin-and-opium
#4
Majede Rezaei, Mostafa Saadat
Relationship between glutathione S-transferase P1 (GSTP1, OMIM: 134660) variants and the risk of drug dependency is unknown. Chronic use of illegal drugs leads to oxidative stress, which can be alleviated by cellular detoxification mechanisms. There are several polymorphisms in the GSTP1, including Ile105Val (rs1695). This polymorphism leads to an Ile105Val amino acid change and may alter the GSTP1 enzyme activity. There is no study on the association between this polymorphism and risks of heroin (HD) or opium (OD) dependency...
August 18, 2018: Biochemical Genetics
https://www.readbyqxmd.com/read/30121880/pharmacological-evaluation-of-tak-828f-a-novel-orally-available-ror%C3%AE-t-inverse-agonist-on-murine-colitis-model
#5
Keiko Igaki, Yoshiki Nakamura, Yusaku Komoike, Keiko Uga, Akira Shibata, Yoshimasa Ishimura, Masashi Yamasaki, Yasuhiro Tsukimi, Noboru Tsuchimori
IL-17-producing Th17 cells and IFN-γ and IL-17 double-producing Th1/17 cells have been identified as the pathogenic cells in inflammatory bowel disease (IBD). Retinoic acid-related orphan receptor γt (RORγt) is a master regulator for the differentiation and activation of Th17 and Th1/17 cells. We discovered a novel orally available TAK-828F, a strong and selective RORγt inverse agonist. To assess the potential of RORγt blockade in the therapy for IBD, the efficacy of TAK-828F in activated T cell transfer mouse colitis model was investigated...
August 18, 2018: Inflammation
https://www.readbyqxmd.com/read/30121736/acute-blood-pressure-management-in-acute-ischemic-stroke-and-spontaneous-cerebral-hemorrhage
#6
REVIEW
Mollie McDermott, Cemal B Sozener
PURPOSE OF REVIEW: We discuss the evidence and guidelines for acute blood pressure (BP) management for patients presenting with acute ischemic stroke or spontaneous cerebral hemorrhage. RECENT FINDINGS: Observational data suggest that the extremes of BP should be avoided in patients presenting with acute ischemic stroke. There is no convincing evidence that active BP reduction results in improved outcomes for ischemic stroke patients. Current guidelines recommend that BP be maintained ≤ 185/110 mmHg in patients who are candidates for intravenous tissue plasminogen activator (IV tPA) or mechanical thrombectomy and that BP be maintained ≤ 180/105 mmHg for at least 24 h in patients who have received IV tPA or have undergone mechanical thrombectomy...
August 18, 2018: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/30121730/variety-is-the-spice-of-life-how-to-explore-a-redox-dependent-heterogeneity-in-genomically-identical-cellular-populations
#7
Meytal Radzinski, Dana Reichmann
Cellular heterogeneity is a widespread phenomenon, existing across organisms and serving a crucial role in evolution and cell survival. Genetically identical cells may as a result present in a variety of forms with different gene and protein expressions, as well as oxidation level. As a result, a wide range of methodologies and techniques for dissecting different types of genetic, proteomic, and phenotypic heterogeneous traits have emerged in recent years in an effort to better understand how diversity exists within a single population and its effects therein...
August 18, 2018: Current Genetics
https://www.readbyqxmd.com/read/30121710/an-insight-into-paracetamol-and-its-metabolites-using-molecular-docking-and-molecular-dynamics-simulation
#8
Yuanqiang Wang, Weiwei Lin, Nan Wu, Xibing He, Junmei Wang, Zhiwei Feng, Xiang-Qun Xie
Paracetamol is a relatively safe analgesia/antipyretic drug without the risks of addiction, dependence, tolerance, and withdrawal when used alone. However, when administrated in an opioid/paracetamol combination product, which often contains a large quantity of paracetamol, it can be potentially dangerous due to the risk of hepatotoxicity. Paracetamol is known to be metabolized into N-(4-hydroxyphenyl)-arachidonamide (AM404) via fatty acid amide hydrolase (FAAH) and into N-acetyl-p-benzoquinone imine (NAPQI) via cytochrome P450 (CYP) enzymes...
August 18, 2018: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/30121575/adipocyte-hdac4-activation-leads-to-beige-adipocyte-expansion-and-reduced-adiposity
#9
Esther Paulo, Dongmei Wu, Peter A Hecker, Yun Zhang, Biao Wang
Numerous studies have suggested that beige adipocyte abundance is correlated with improved metabolic performance, but direct evidence showing that beige adipocyte expansion protects animals from the development of obesity is missing. Previously, we have described that the Liver kinase b1 (Lkb1) regulates beige adipocyte renaissance in subcutaneous inguinal white adipose tissue (iWAT) through a class IIa histone deacetylase 4 (HDAC4)-dependent mechanism. This study investigates the physiological impact of persistent beige adipocyte renaissance in energy homeostasis in mice...
August 18, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/30121515/risk-of-de-novo-infection-following-acute-kidney-injury-a-retrospective-cohort-study
#10
Amélie Bernier-Jean, William Beaubien-Souligny, Thierry Ducruet, Anatolie Duca, Martin Albert, Valéry Lavergne, Josée Bouchard
PURPOSE: Recent studies suggest that acute kidney injury (AKI) can affect distant organ function and increase non-renal complications. We determined whether AKI is associated with an increased risk of incident infections. MATERIAL AND METHODS: We conducted a one-year single-center retrospective cohort study, excluding patients readmitted to the ICU or for <24 h, on chronic dialysis, and kidney transplant recipients. The primary outcome was the development of incident infections analyzed by multivariate time-dependent Cox models...
August 8, 2018: Journal of Critical Care
https://www.readbyqxmd.com/read/30121499/lipid-metabolism-disorder-induced-by-up-regulation-of-mir-125b-and-mir-144-following-%C3%AE-diketone-antibiotic-exposure-to-f0-zebrafish-danio-rerio
#11
Xuedong Wang, Yuansi Zheng, Yan Ma, Liyang Du, Fangyu Chu, Haidong Gu, Randy A Dahlgren, Yanyan Li, Huili Wang
β-Diketone antibiotics (DKAs) are widely used in human and veterinary medicine to prevent and treat a large variety of infectious diseases. Long-term DKA exposure to zebrafish can result in lipid metabolism disorders and liver function abnormalities. Based on our previous miRNA-seq analyses, miR-144 and miR-125b were identified as target genes regulating lipid metabolism. DKA-exposure at 12.5 and 25 mg/L significantly increased the expressions of miR-144 and miR-125b. The expression levels for the two miRNAs exhibited an inverse relationship with their lipid-metabolism-related target genes (ppardb, bcl2a, pparaa and pparda)...
August 16, 2018: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/30121486/chronic-toxicity-of-an-environmentally-relevant-and-equitoxic-ratio-of-five-metals-to-two-antarctic-marine-microalgae-shows-complex-mixture-interactivity
#12
Darren J Koppel, Merrin S Adams, Catherine K King, Dianne F Jolley
Metal contaminants are rarely present in the environment individually, yet environmental quality guidelines are derived from single-metal toxicity data. Few metal mixture studies have investigated more than binary mixtures and many are at unrealistically high effect concentrations to freshwater organisms. This study investigates the toxicity of five metals (Cd, Cu, Ni, Pb, and Zn) to the Antarctic marine microalgae Phaeocystis antarctica and Cryothecomonas armigera. Two mixtures were tested: (i) an equitoxic mixture of contaminants present at their single-metal EC10 concentrations, and (ii) an environmental mixture based on the ratio metal concentrations in a contaminated Antarctic marine bay...
July 25, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/30121414/synthesis-of-three-deoxy-sophorose-derivatives-for-evaluating-the-requirement-of-hydroxy-groups-at-position-3-and-or-3-of-sophorose-by-1-2-%C3%AE-oligoglucan-phosphorylases
#13
Nobukiyo Tanaka, Masahiro Nakajima, Hiroki Aramasa, Hiroyuki Nakai, Hayao Taguchi, Wakako Tsuzuki, Shiro Komba
Sophorose (Sop2 ) is known as a powerful inducer of cellulases in Trichoderma reesei, and in recent years 1,2-β-D-oligoglucan phosphorylase (SOGP) has been found to use Sop2 in synthetic reactions. From the structure of the complex of SOGP with Sop2 , it was predicted that both the 3-hydroxy group at the reducing end glucose moiety of Sop2 and the 3'-hydroxy group at the non-reducing end glucose moiety of Sop2 were important for substrate recognition. In this study, three kinds of 3- and/or 3'-deoxy-Sop2 derivatives were synthesized to evaluate this mechanism...
August 12, 2018: Carbohydrate Research
https://www.readbyqxmd.com/read/30121400/vanadyl-complexes-discriminate-between-neuroblastoma-cells-and-primary-neurons-by-inducing-cell-specific-apoptotic-pathways
#14
Yue Zhang, Lichao Wang, Kewu Zeng, Kui Wang, Xiaoda Yang
Vanadium compounds have arisen as potential therapeutic agent for the treatment of cancers over the past decades. A few studies suggested that vanadyl complexes may discriminate between the cancerous and the normal cells. Here, we reported the investigation on the pro-apoptotic effect and the underlying mechanism of bis(acetylacetonato) oxovanadium(IV) ([VO(acac)2 ]) on SH-SY5Y neuroblastoma cells in comparison with that of mouse primary cortex neurons. The experimental results revealed that [VO(acac)2 ] showed about 10-fold higher cytotoxicity (IC50 ~16 μM) on the neuroblastoma cells than on normal neurons (IC50 ~250 μM)...
August 3, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/30121340/pb-inhibits-hippocampal-synaptic-transmission-via-cyclin-dependent-kinase-5-dependent-synapsin-1-phosphorylation
#15
Jin-Jun Ding, Rong-Xin Zou, Hui-Ming He, Zhi-Yi Lou, Yi Xu, Hui-Li Wang
Lead (Pb) exposure impairs the nervous system, of which the injury of cognitive development is obvious. But the mechanism of Pb induced disorders of neuro-transmission remain elusive. In this study, primary hippocampal neurons were exposed to Pb at the dosage of 5 μM from days in vitro (DIV) 3 to DIV14 and the electrophysiological recordings were performed at DIV14. Sprague-Dawley (SD) rat pups were exposed to Pb from parturition to weaning indirectly from their mothers whose drinking water containing 250 ppm Pb, then directly exposed to Pb at the dosage of 250 ppm from postnatal day (PND) 21 to PND30...
August 16, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/30121303/removal-of-heavy-metal-chromium-using-cross-linked-chitosan-composite-nanofiber-mats
#16
Minjuan Jiang, Tong Han, Jinhu Wang, Linjun Shao, Chenze Qi, Xian M Zhang, Chunli Liu, Xuejing Liu
Uniform chitosan composite nanofiber mats (CS/PAAS) containing 4.0 wt% polyacrylic acid sodium loading have been prepared by electrospinning, followed by annealing at elevated temperature to improve solvent resistance and mechanical strength. The CS/PAAS nanofiber mats have been characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR) and tensile strength analysis. The prepared nanofiber mats have been shown to be much better than the pristine chitosan powder to adsorb the chromium (VI) ion...
August 16, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/30121255/helminth-antigen-conditioned-dendritic-cells-generate-anti-inflammatory-cd4-t-cells-independent-of-antigen-presentation-via-mhc-ii
#17
Chelsea Elizabeth Matisz, Markus Bruno Geuking, Fernando Lopes, Björn Petri, Arthur Wang, Keith Alexander Sharkey, Derek Mark McKay
A recently identified feature of the host response to infection with helminth parasites is the suppression of concomitant disease. Dendritic cells (DC) exposed to antigens from the tapeworm Hymenolepis diminuta significantly reduce the severity of dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice. Here we elucidate mechanisms underlying the beneficial effects of this cellular immunotherapy. We show a requirement for CCR7 expression on transferred H. diminuta antigen-treated DCs (HD-DCs), suggesting homing to secondary lymphoid tissues is important for suppression of colitis...
August 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/30121250/jnk-akt-nf-%C3%AE%C2%BAb-controls-p-glycoprotein-expression-to-attenuate-the-cytotoxicity-of-deoxynivalenol-in-mammalian-cells
#18
Xiaoming Li, Peiqiang Mu, Han Qiao, Jikai Wen, Yiqun Deng
P-glycoprotein (P-gp) plays critical roles in mediating the cytotoxicity of many drugs that are P-gp substrates. Previously, we reported that P-glycoprotein (P-gp) is the foremost efflux transporter of deoxynivalenol (DON), which is one of the most abundant mycotoxins. However, whether DON changes the expression of P-gp and its mechanism are still unclear. In this study, we found DON can induce the mRNA and protein levels of P-gp in a time- and dose-dependent manner. Mechanistically, the upregulation of P-gp expression is attributable to the induction of DON-induced proapoptotic pathways as reflected by the c-Jun N-terminal kinases (JNK) phosphorylation, AKT phosphorylation and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation to the nucleus...
August 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30121235/topical-application-of-stem-bark-ethanol-extract-of-sonapatha-oroxylum-indicum-l-kurz-accelerates-healing-of-deep-dermal-excision-wound-in-swiss-albino-mice
#19
K Lalrinzuali, M Vabeiryureilai, Ganesh Chandra Jagetia
ETHNOPHARMACOLOGICAL RELEVANCE: The Oroxylum indicum is used traditionally to treat fever, colic, stomach ulcers, constipation, indigestion, intestinal worms, strangury, asthma, cough, hiccough, diarrhea, dysentery and wounds by the herbal healers of Mizoram and it is also part of Ayurvedic formulations. AIMS OF THE STUDY: The wound healing activity of Oroxylum indicum has not been investigated therefore the present study was undertaken to evaluate the ability of different concentrations of ethanol extract of stem bark of Oroxylum indicum in the deep dermal excision wounds of mice...
August 16, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/30121181/the-impact-of-multipole-pacing-on-left-ventricular-function-in-patients-with-cardiac-resynchronization-therapy-a-real-time-three-dimensional-echocardiography-approach
#20
Severin Weigand, Michael Karl, Amir Brkić, Carsten Lennerz, Christian Grebmer, Patrick Blažek, Marielouise Kornmayer, Claudia Schaarschmidt, Lorraine Wesemann, Tilko Reents, Gabriele Hessling, Isabel Deisenhofer, Christof Kolb
BACKGROUND: Cardiac resynchronization therapy (CRT) is standard of care in heart failure (HF), however this technique is associated with a non-responder rate of 30%. Multipole pacing (MPP) with a quadripolar lead may optimize CRT and responder rate by creating two electrical wave fronts in the left ventricular (LV) myocardium simultaneously in order to reduce mechanical dyssynchrony. The objective of this study was to investigate the acute impact of MPP on LV function by assessing systolic dyssynchrony index (SDI) and left ventricular ejection fraction (LVEF) via real-time three-dimensional echocardiography (RT3DE)...
August 15, 2018: International Journal of Cardiology
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