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https://www.readbyqxmd.com/read/28944315/is-chronic-ahr-activation-by-rapidly-metabolized-ligands-safe-for-the-treatment-of-immune-mediated-diseases
#1
Allison K Ehrlich, Nancy I Kerkvliet
There is a long standing perception that AhR ligands are automatically disqualified from pharmaceutical development due to their induction of Cyp1a1 as well as their potential for causing "dioxin-like" toxicities. However, recent discoveries of new AhR ligands with potential therapeutic applications have been reported, inviting reconsideration of this policy. One area of exploration is focused on the activation of AhR to promote the generation of regulatory T cells, which control the intensity and duration of immune responses...
February 2017: Current Opinion in Toxicology
https://www.readbyqxmd.com/read/28942254/characterization-of-pcdd-fs-and-dioxin-like-pcbs-emitted-from-two-woodchip-boilers-in-taiwan
#2
Shih Ting Bai, Shu Hao Chang, Jing Min Duh, Fu Hsiang Sung, Jhen Sheng Su, Moo Been Chang
This study investigates the formation and removal of PCDD/Fs and dl-PCBs in two woodchips boilers during different operating periods. Results indicate that combustion condition affects PCDD/F and dl-PCB formation within the woodchip combustion process. PCDD/F and dl-PCB concentrations during the start-up period are much higher than those measured during normal operation and shut-down periods due to unstable combustion. PCDD/F and dl-PCB concentrations at APCDs inlet of Plant A are significantly higher than that of Plant B due to the lower combustion temperature (500-850 °C) compared with Plant B (850-925 °C)...
September 18, 2017: Chemosphere
https://www.readbyqxmd.com/read/28942070/ryanodine-receptor-and-fk506-binding-protein-1-in-the-atlantic-killifish-fundulus-heteroclitus-a-phylogenetic-and-population-based-comparison
#3
Erika B Holland, Jared V Goldstone, Isaac N Pessah, Andrew Whitehead, Noah M Reid, Sibel I Karchner, Mark E Hahn, Diane E Nacci, Bryan W Clark, John J Stegeman
Non-dioxin-like polychlorinated biphenyls (NDL PCBs) activate ryanodine receptors (RyR), microsomal Ca(2+) channels of broad significance. Teleost fish may be important models for NDL PCB neurotoxicity, and we used sequencing databases to characterize teleost RyR and FK506 binding protein 12 or 12.6kDa (genes FKBP1A; FKBP1B), which promote NDL PCB-triggered Ca(2+) dysregulation. Particular focus was placed on describing genes in the Atlantic killifish (Fundulus heteroclitus) genome and searching available RNA-sequencing datasets for single nucleotide variants (SNV) between PCB tolerant killifish from New Bedford Harbor (NBH) versus sensitive killifish from Scorton Creek (SC), MA...
September 4, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28936204/modulatory-influence-of-segmented-filamentous-bacteria-on-transcriptomic-response-of-gnotobiotic-mice-exposed-to-tcdd
#4
Robert D Stedtfeld, Benli Chai, Robert B Crawford, Tiffany M Stedtfeld, Maggie R Williams, Shao Xiangwen, Tomomi Kuwahara, James R Cole, Norbert E Kaminski, James M Tiedje, Syed A Hashsham
Environmental toxicants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor (AhR), are known to induce host toxicity and structural shifts in the gut microbiota. Key bacterial populations with similar or opposing functional responses to AhR ligand exposure may potentially help regulate expression of genes associated with immune dysfunction. To examine this question and the mechanisms for AhR ligand-induced bacterial shifts, C57BL/6 gnotobiotic mice were colonized with and without segmented filamentous bacteria (SFB) - an immune activator...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28932453/crystal-structure-of-ethyl-ene-dioxy-tetra-thia-fulvalene-4-5-bis-thiol-benzoic-acid-0-25-hydrate
#5
Yuanyuan Zhang, Qiqian He, Huijie Bao, Lejia Wang, Xunwen Xiao
In the title compound (systematic name: 4,4'-{[2-(5,6-di-hydro-[1,3]di-thiolo[4,5-b][1,4]dioxin-2-yl-idene)-1,3-di-thiole-4,5-di-yl]bis-(sulfanedi-yl)}di-benzoic acid 0.25-hydrate), C22H14O6S6·0.25H2O, the tetra-thia-fulvalene (TTF) core adopts a boat conformation, where the central S2C=CS2 plane makes dihedral angles of 31.34 (4) and 26.83 (6)°, respectively, with the peripheral S2C=CS2 and S2C2O2 planes. In the crystal, the benzoic acid mol-ecules are linked via O-H⋯O hydrogen bonds, forming inversion dimers with R2(2)(8) motifs...
September 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28925692/occurrence-of-natural-mixed-halogenated-dibenzo-p-dioxins-specific-distribution-and-profiles-in-mussels-from-seto-inland-sea-japan
#6
Akitoshi Goto, Nguyen Minh Tue, Masayuki Someya, Tomohiko Isobe, Shin Takahashi, Shinsuke Tanabe, Tatsuya Kunisue
In addition to unintentional formation of polychlorinated (PCDD/Fs), polybrominated (PBDD/Fs) and mixed halogenated (PXDD/Fs) dibenzo-p-dioxins/dibenzofurans during industrial activities, recent studies have shown that several PBDD and PXDD congeners can be produced by marine algal species from the coastal environment. However, multiple exposure status of anthropogenic and naturally-derived dioxins in marine organisms remains unclear. The present study examined the occurrence, geographical distribution and potential sources of PCDD/Fs, PBDD/Fs and PXDD/Fs using mussels and brown algae collected in 2012 from Seto Inland Sea, Japan...
September 19, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28923513/a-dioxin-like-compound-induces-hyperplasia-and-branching-morphogenesis-in-mouse-mammary-gland-through-alterations-in-tgf-%C3%AE-1-and-aryl-hydrocarbon-receptor-signaling
#7
Miret Noelia, Rico-Leo Eva, Pontillo Carolina, Zotta Elsa, Fernández-Salguero Pedro, Randi Andrea
Hexachlorobenzene (HCB) is a widespread environmental pollutant and a dioxin-like compound that binds weakly to the aryl hydrocarbon receptor (AhR). Because AhR and transforming growth factor β1 (TGF-β1) converge to regulate common signaling pathways, alterations in this crosstalk might contribute to developing preneoplastic lesions. The aim of this study was to evaluate HCB action on TGF-β1 and AhR signaling in mouse mammary gland, through AhR+/+ and AhR-/- models. Results showed a differential effect in mouse mammary epithelial cells (NMuMG), depending on the dose: 0...
September 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28922406/loss-of-liver-specific-and-sexually-dimorphic-gene-expression-by-aryl-hydrocarbon-receptor-activation-in-c57bl-6-mice
#8
Rance Nault, Kelly A Fader, Jack R Harkema, Tim Zacharewski
The aryl hydrocarbon receptor (AhR) is a highly conserved transcription factor that mediates a broad spectrum of species-, strain-, sex-, age-, tissue-, and cell-specific responses elicited by structurally diverse ligands including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Dose-dependent effects on liver-specific and sexually dimorphic gene expression were examined in male and female mice gavaged with TCDD every 4 days for 28 or 92 days. RNA-seq data revealed the coordinated repression of 181 genes predominately expressed in the liver including albumin (3...
2017: PloS One
https://www.readbyqxmd.com/read/28922086/assessment-of-ah-receptor-transcriptional-activity-mediated-by-halogenated-dibenzo-p-dioxins-and-dibenzofurans-pxdd-fs-in-human-and-mouse-cell-systems
#9
Kari L Organtini, Troy D Hubbard, Gary H Perdew, Frank L Dorman
Polybrominated and mixed bromo/chloro dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) are emerging environmental contaminants of concern. Thus far, an understanding of the toxicological behavior of these chemical species and their impact upon human health is incomplete. Here we utilized human and mouse hepatocellular carcinoma cell lines to examine the ability of differentially halogenated PXDD/F congeners to induce aryl hydrocarbon receptor (AHR)-mediated transcriptional activity. Dose-response experiments in reporter cell lines identified varied potencies among differentially halogenated PXDD/F isomers by comparison of EC50 values relative to the prototypical AHR agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)...
September 18, 2017: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
https://www.readbyqxmd.com/read/28915320/adipose-tissue-as-a-site-of-toxin-accumulation
#10
Erin Jackson, Robin Shoemaker, Nika Larian, Lisa Cassis
We examine the role of adipose tissue, typically considered an energy storage site, as a potential site of toxicant accumulation. Although the production of most persistent organic pollutants (POPs) was banned years ago, these toxicants persist in the environment due to their resistance to biodegradation and widespread distribution in various environmental forms (e.g., vapor, sediment, and water). As a result, human exposure to these toxicants is inevitable. Largely due to their lipophilicity, POPs bioaccumulate in adipose tissue, resulting in greater body burdens of these environmental toxicants with obesity...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28913580/in-vitro-tools-for-the-toxicological-evaluation-of-sediments-and-dredged-materials-intra-and-inter-laboratory-comparisons-of-chemical-and-bioanalytical-methods
#11
Kathrin Eichbaum, Markus Brinkmann, Leonie Nuesser, Carolin Gembé, Marina Ohlig, Sebastian Buchinger, Georg Reifferscheid, Markus Hecker, John P Giesy, Henner Hollert
The implementation of in vitro bioassays for the screening of dioxin-like compounds (DLCs) into management guidelines of dredged material is of increasing interest to regulators and risk assessors. This study reports on an intra- and inter-laboratory comparison study between four independent laboratories. A bioassay battery consisting of RTL-W1 (7-ethoxy-resorufin-O-deethylase; EROD), H4IIE (micro-EROD), and H4IIE-luc cells was used to assess aryl hydrocarbon receptor-mediated effects of sediments from two major European rivers, differently contaminated with DLCs...
September 14, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28910589/persistent-organic-pollutants-and-related-biological-responses-measured-in-coastal-fish-using-chemical-and-biological-screening-methods
#12
Zhanna Tairova, Jakob Strand, Rossana Bossi, Martin M Larsen, Lars Förlin, Anders Bignert, Jenny Hedman, Jens Gercken, Thomas Lang, Nicolai F Fricke, Gert Asmund, Manhai Long, Eva C Bonefeld-Jørgensen
The aim of this study was to investigate the spatial distribution, levels of dioxin-like compounds (DLC), and biological responses in two fish species. The viviparous eelpout (Zoarces viviparus) was collected from various locations in the Baltic Sea and in fjords of Kattegat and Skagerrak, while shorthorn sculpin (Myoxocephalus scorpius) was obtained at the polychlorinated biphenyl (PCB) polluted site in North West Greenland. Significant differences were detected both in contaminant levels and relative contributions from either polychlorinated dibenzodioxins (PCDD) or polychlorinated dibenzofurans (PCDF or furans) and mono-ortho- and non-ortho (coplanar) polychlorinated biphenyls (dl-PCB)...
September 14, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28904354/identification-and-characterization-of-the-novel-reversible-and-selective-cathepsin-x-inhibitors
#13
Urša Pečar Fonović, Ana Mitrović, Damijan Knez, Tanja Jakoš, Anja Pišlar, Boris Brus, Bojan Doljak, Jure Stojan, Simon Žakelj, Jurij Trontelj, Stanislav Gobec, Janko Kos
Cathepsin X is a cysteine peptidase involved in the progression of cancer and neurodegenerative diseases. Targeting this enzyme with selective inhibitors opens a new possibility for intervention in several therapeutic areas. In this study triazole-based reversible and selective inhibitors of cathepsin X have been identified. Their selectivity and binding is enhanced when the 2,3-dihydrobenzo[b][1,4]dioxine moiety is present as the R(1) substituent. Of a series of selected triazole-benzodioxine derivatives, compound 22 is the most potent inhibitor of cathepsin X carboxypeptidase activity (Ki = 2...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28904176/the-crystal-structure-of-the-ahrr-arnt-heterodimer-reveals-the-structural-basis-of-the-repression-of-ahr-mediated-transcription
#14
Shunya Sakurai, Toshiyuki Shimizu, Umeharu Ohto
2,3,7,8-Tetrachlorodibenzo-p-dioxin and related compounds (TCDDs) are extraordinarily potent environmental toxic pollutants. Most of the TCDD toxicities are mediated by aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor belonging to the basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) family. Upon ligand binding, AhR forms a heterodimer with AhR nuclear translocator (ARNT) and induces the expression of genes involved in various biological responses. One of the genes induced by AhR encodes AhR repressor (AhRR), which also forms a heterodimer with ARNT and represses the activation of AhR-dependent transcription...
September 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28898957/persistent-organic-pollutants-in-krill-from-the-bellingshausen-south-scotia-and-weddell-seas
#15
Cristóbal J Galbán-Malagón, Gema Hernán, Esteban Abad, Jordi Dachs
Persistent organic pollutants (POPs) reach Antarctica through atmospheric transport, oceanic currents, and to minor extent, by migratory animals. The Southern Ocean is a net sink for many POPs, with a key contribution of the settling fluxes of POPs bound to organic matter (biological pump). However, little is known about POP transfer through the food web in the Southern Ocean and Antarctic waters, where krill is an important ecological node. In this study, we assessed the occurrence of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) in Antarctic krill (Euphausia superba) from the Bellingshausen, South Scotia and Weddell Seas around the Antarctic Peninsula...
September 8, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28898780/characteristics-of-pcdds-pcdfs-in-stack-gas-from-medical-waste-incinerators
#16
Young Wook Yoon, Tae-Wan Jeon, Jun-Ik Son, Kyu-Yeon Kim, Eun-Hye Kwon, Sun-Kyoung Shin, Jun-Gu Kang
Toxic polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in 45 stack gas samples were measured from 19 medical waste incinerators in South Korea using high-resolution gas chromatography equipped with a high-resolution mass spectrometer. The average concentrations of the sum of 17 toxic PCDD/PCDF congeners emitted from the medical waste incinerators ranged from 0.153 to 101.9 ng/Sm(3). Based on the World Health Organization toxic equivalency factor, they ranged from 0.007 to 5...
September 6, 2017: Chemosphere
https://www.readbyqxmd.com/read/28898241/alterations-in-the-programming-of-energy-metabolism-in-adolescents-with-background-exposure-to-dioxins-dl-pcbs-and-pbdes
#17
Marike M Leijs, Janna G Koppe, Thomas Vulsma, Kees Olie, Wim M C van Aalderen, Pim de Voogt, Juliette Legler, Gavin W Ten Tusscher
OBJECTIVES: Dioxins and PCBs are highly toxic and persistent environmental pollutants that are measurable in humans worldwide. These persistent organic pollutants are associated with a higher incidence of diabetes mellitus. We hypothesise that perinatal (background) exposure to industrial pollutants like dioxins also influences body mass development and energy metabolism in later life. STUDY DESIGN: In The Netherlands, the perinatal exposure (prenatal exposure and postnatal lactational intake) to dioxins has been studied prospectively since 1987...
2017: PloS One
https://www.readbyqxmd.com/read/28892854/tissue-distribution-and-maternal-transfer-of-persistent-organic-pollutants-in-kentish-plovers-charadrius-alexandrines-from-cangzhou-wetland-bohai-bay-china
#18
Shucheng Zheng, Pu Wang, Huizhong Sun, Julius Matsiko, Yanfen Hao, Derong Meng, Yingming Li, Guogang Zhang, Qinghua Zhang, Guibin Jiang
Several persistent organic pollutants, including polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs), were comprehensively investigated in the egg, muscle and liver samples of Kentish Plover (Charadrius alexandrines) collected from Cangzhou Wetland in western Bohai Bay, China. DDTs were the most abundant contaminants (35.4-9853ngg(-1) lipid weight, lw), followed by HCHs, PCBs, PBDEs and HCB...
September 7, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28891521/effects-of-high-fat-diet-and-perinatal-dioxin-exposure-on-development-of-body-size-and-expression-of-platelet-derived-growth-factor-receptor-%C3%AE-in-the-rat-brain
#19
Amartuvshin Bor, Muneko Nishijo, Hiroshi Nishimaru, Tomoya Nakamura, Nghi Ngoc Tran, Quang Van Le, Yusaku Takamura, Jumpei Matsumoto, Yoshikazu Nishino, Hisao Nishijo
Environmental exposure to dioxins, consumption of a high fat diet, and platelet-derived growth factor receptor β signaling in the brain affect feeding behavior, which is an important determinant of body growth. In the present study, we investigated the effects of prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and high fact diet after weaning on body growth and expression of platelet-derived growth factor receptor β in the brain in rat pups. Subjects from the control and dioxin exposure groups were assigned to 1 of 3 different diet groups: standard diet, high fat diet in the juvenile period, or high fat diet in adulthood...
2017: Journal of Integrative Neuroscience
https://www.readbyqxmd.com/read/28889025/industrial-pollution-and-cancer-in-spain-an-important-public-health-issue
#20
Pablo Fernández-Navarro, Javier García-Pérez, Rebeca Ramis, Elena Boldo, Gonzalo López-Abente
Cancer can be caused by exposure to air pollution released by industrial facilities. The European Pollutant Release and Transfer Register (E-PRTR) has made it possible to study exposure to industrial pollution. This study seeks to describe the industrial emissions in the vicinity of Spanish towns and their temporal changes, and review our experience studying industrial pollution and cancer. Data on industrial pollutant sources (2007-2010) were obtained from the E-PRTR registries. Population exposure was estimated by the distance from towns to industrial facilities...
September 7, 2017: Environmental Research
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