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https://www.readbyqxmd.com/read/28100006/the-fingerprint-of-antimitochondrial-antibodies-and-the-etiology-of-primary-biliary-cholangitis
#1
Zongwen Shuai, Jinjun Wang, Madhu Badamagunta, Jinjung Choi, Guoxiang Yang, Weici Zhang, Thomas P Kenny, Kathryn Guggenheim, Mark J Kurth, Aftab A Ansari, John Voss, Ross L Coppel, Pietro Invernizzi, Patrick S C Leung, M Eric Gershwin
The identification of environmental factors that lead to loss of tolerance has been coined the Holy Grail of autoimmunity. Our work has focused on the reactivity of antimitochondrial autoantibodies (AMA) to chemical xenobiotics and has hypothesized that a modified peptide within PDC-E2, the major mitochondrial autoantigen, will have been immunologically recognized at the time of loss of tolerance. Herein we successfully applied intein technology to construct a PDC-E2 protein fragment containing amino acid residues 177-314 of PDC-E2 by joining a recombinant peptide spanning residues 177 to 252 (PDC-228) with a 62 residue synthetic peptide from 253 to 314 (PP), which encompasses PDC-E2 ILD...
January 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28098843/perm-hypothesis-the-fundamental-machinery-able-to-elucidate-the-role-of-xenobiotics-and-hormesis-in-cell-survival-and-homeostasis
#2
REVIEW
Salvatore Chirumbolo, Geir Bjørklund
In this article the Proteasome, Endoplasmic Reticulum and Mitochondria (PERM) hypothesis is discussed. The complex machinery made by three homeostatic mechanisms involving the proteasome (P), endoplasmic reticulum (ER) and mitochondria (M) is addressed in order to elucidate the beneficial role of many xenobiotics, either trace metals or phytochemicals, which are spread in the human environment and in dietary habits, exerting their actions on the mechanisms underlying cell survival (apoptosis, cell cycle regulation, DNA repair and turnover, autophagy) and stress response...
January 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28094042/responses-of-the-rotifer-brachionus-plicatilis-to-flame-retardant-bde-47-stress
#3
Xiaoyang Jian, Xuexi Tang, Ningning Xu, Jingjing Sha, You Wang
A series of short-term toxicological tests were conducted on the rotifer Brachionus plicatilis to assess the toxicity of the flame retardant 2,2',4,4'-tetrabrominated biphenyl ether (BDE-47). BDE-47 increased mortality, morphological damage, and altered population dynamics and fecundity of rotifer. Antioxidant enzymes were differentially changed to maintain the balance between antioxidant and pro-oxidant activity. However, with increases in the concentration of BDE-47, the metabolic and antioxidant activity decreased...
January 13, 2017: Marine Pollution Bulletin
https://www.readbyqxmd.com/read/28092182/an-estrogen-receptor-%C3%AE-selective-agonist-inhibits-non-alcoholic-steatohepatitis-in-preclinical-models-by-regulating-bile-acid-and-xenobiotic-receptors
#4
Suriyan Ponnusamy, Quynh T Tran, Thirumagal Thiyagarajan, Duane D Miller, Dave Bridges, Ramesh Narayanan
Non-alcoholic steatohepatitis (NASH) affects 8-10 million people in the US and up to 75% of obese individuals. Despite this, there are no approved oral therapeutics to treat NASH and therefore the need for novel approaches exists. The estrogen receptor β (ER-β)-selective agonist, β-LGND2, inhibits body weight and white adipose tissue, and increases metabolism, resulting in higher energy expenditure and thermogenesis. Due to favorable effects of β-LGND2 on obesity, we hypothesized that β-LGND2 will prevent NASH directly by reducing lipid accumulation in the liver or indirectly by favorably changing body composition...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28090466/microbiome-linked-crosstalk-in-the-gastrointestinal-exposome-towards-host-health-and-disease
#5
REVIEW
Yuseok Moon
The gastrointestinal exposome represents the integration of all xenobiotic components and host-derived endogenous components affecting the host health, disease progression and ultimately clinical outcomes during the lifespan. The human gut microbiome as a dynamic exposome of commensalism continuously interacts with other exogenous exposome as well as host sentineling components including the immune and neuroendocrine circuit. The composition and diversity of the microbiome are established on the basis of the luminal environment (physical, chemical and biological exposome) and host surveillance at each part of the gastrointestinal lining...
December 2016: Pediatric Gastroenterology, Hepatology & Nutrition
https://www.readbyqxmd.com/read/28089783/characterization-of-rat-or-human-hepatocytes-cultured-in-microphysiological-systems-mps-to-identify-hepatotoxicity
#6
Shih-Yu Chang, Jenna L Voellinger, Kirk P Van Ness, Brian Chapron, Rachel M Shaffer, Thomas Neumann, Collin C White, Terrance J Kavanagh, Edward J Kelly, David L Eaton
The liver is the main site for drug and xenobiotics metabolism, including inactivation or bioactivation. In order to improve the predictability of drug safety and efficacy in clinical development, and to facilitate the evaluation of the potential human health effects from exposure to environmental contaminants, there is a critical need to accurately model human organ systems such as the liver in vitro. We are developing a microphysiological system (MPS) based on a new commercial microfluidic platform (Nortis, Inc...
January 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28089504/review-nutrient-sulfate-supply-from-mother-to-fetus-placental-adaptive-responses-during-human-and-animal-gestation
#7
REVIEW
P A Dawson, K Richard, A Perkins, Z Zhang, D G Simmons
Nutrient sulfate has numerous roles in mammalian physiology and is essential for healthy fetal growth and development. The fetus has limited capacity to generate sulfate and relies on sulfate supplied from the maternal circulation via placental sulfate transporters. The placenta also has a high sulfate requirement for numerous molecular and cellular functions, including sulfate conjugation (sulfonation) to estrogen and thyroid hormone which leads to their inactivation. Accordingly, the ratio of sulfonated (inactive) to unconjugated (active) hormones modulates endocrine function in fetal, placental and maternal tissues...
January 4, 2017: Placenta
https://www.readbyqxmd.com/read/28088650/assessing-the-identity-and-expression-level-of-the-cytochrome-p450-20a1-cyp20a1-gene-in-the-bpa-bde-47-and-waf-exposed-copepods-tigriopus-japonicus-and-paracyclopina-nana
#8
Jeonghoon Han, Duck-Hyun Kim, Jung Soo Seo, Il-Chan Kim, David R Nelson, Jayesh Puthumana, Jae-Seong Lee
CYP20A1 is a member of the cytochrome P450 (CYP) superfamily, identified as an orphan P450 without any assigned biological function; hence, its continued status as an "orphan" gene. In order to address this shortcoming in our understanding of this superfamily, we sought to characterize the CYP20A1 gene in the copepods Tigriopus japonicus (Tj-CYP20A1) and Paracyclopina nana (Pn-CYP20A1) at their mRNA transcriptional level. We assessed the response of this gene's expression in various developmental stages and in response to treatment with bisphenol A (BPA), 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47), and water accommodated fractions (WAFs) of crude oil...
January 11, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28088094/organ-on-a-chip-for-assessing-environmental-toxicants
#9
REVIEW
Soohee Cho, Jeong-Yeol Yoon
Man-made xenobiotics, whose potential toxicological effects are not fully understood, are oversaturating the already-contaminated environment. Due to the rate of toxicant accumulation, unmanaged disposal, and unknown adverse effects to the environment and the human population, there is a crucial need to screen for environmental toxicants. Animal models and in vitro models are ineffective models in predicting in vivo responses due to inter-species difference and/or lack of physiologically-relevant 3D tissue environment...
January 11, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28077779/embryonic-exposure-to-tcdd-impacts-osteogenesis-of-the-axial-skeleton-in-japanese-medaka-oryzias-latipes
#10
AtLee T D Watson, Antonio Planchart, Carolyn J Mattingly, Christoph Winkler, David M Reif, Seth W Kullman
Recent studies from mammalian, fish, and in vitro models have identified bone and cartilage development as sensitive targets for dioxins and other aryl hydrocarbon receptor ligands. In this study, we assess how embryonic 2,3,7,8-tetrachlorochlorodibenzo-p-dioxin (TCDD) exposure impacts axial osteogenesis in Japanese medaka (Oryzias latipes), a vertebrate model of human bone development. Embryos from inbred wild-type Orange-red Hd-dR and 3 transgenic medaka lines (twist:EGFP, osx/sp7:mCherry, col10a1:nlGFP) were exposed to 0...
November 15, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28074615/a-database-of-optimized-proteomic-quantitative-methods-for-284-human-drug-disposition-related-proteins-for-applications-in-pbpk-modeling
#11
Marc Vrana, Dale Whittington, Vivek Nautiyal, Bhagwat Prasad
The aim of this study was to create an open access repository of validated LC-MS/MS (MRM) methods for quantifying 284 important proteins associated with drug absorption, distribution, metabolism and excretion (ADME). Various in silico and experimental approaches were used to select surrogate peptides and optimize instrument parameters for LC-MS/MS quantification of the selected proteins. The final methods were uploaded to an online public database (ADME QPrOmics(TM); www.qpromics.uw.edu/qpromics/assay/) which provides essential information for facile method development in triple quadrupole MS instruments...
January 11, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28073050/genome-wide-identification-of-atp-binding-cassette-abc-transporters-and-their-roles-in-response-to-polycyclic-aromatic-hydrocarbons-pahs-in-the-copepod-paracyclopina-nana
#12
Chang-Bum Jeong, Duck-Hyun Kim, Hye-Min Kang, Young Hwan Lee, Hui-Su Kim, Il-Chan Kim, Jae-Seong Lee
The ATP-binding cassette (ABC) protein superfamily is one of the largest gene families and is highly conserved in all domains. The ABC proteins play roles in several biological processes, including multi-xenobiotic resistance (MXR), by functioning as transporters in the cellular membrane. They also mediate the cellular efflux of a wide range of substrates against concentration gradients. In this study, 37 ABC genes belonging to eight distinct subfamilies were identified in the marine copepod Paracyclopina nana and annotated based on a phylogenetic analysis...
December 30, 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/28072829/predicting-the-metabolic-sites-by-flavin-containing-monooxygenase-on-drug-molecules-using-svm-classification-on-computed-quantum-mechanics-and-circular-fingerprints-molecular-descriptors
#13
Chien-Wei Fu, Thy-Hou Lin
As an important enzyme in Phase I drug metabolism, the flavin-containing monooxygenase (FMO) also metabolizes some xenobiotics with soft nucleophiles. The site of metabolism (SOM) on a molecule is the site where the metabolic reaction is exerted by an enzyme. Accurate prediction of SOMs on drug molecules will assist the search for drug leads during the optimization process. Here, some quantum mechanics features such as the condensed Fukui function and attributes from circular fingerprints (called Molprint2D) are computed and classified using the support vector machine (SVM) for predicting some potential SOMs on a series of drugs that can be metabolized by FMO enzymes...
2017: PloS One
https://www.readbyqxmd.com/read/28071785/bioactive-polyphenols-and-cardiovascular-disease-chemical-antagonists-pharmacological-agents-or-xenobiotics-that-drive-an-adaptive-response
#14
REVIEW
Katarzyna Goszcz, Garry G Duthie, Derek Stewart, Stephen J Leslie, Ian L Megson
Polyphenols are widely regarded to have a wide range of health-promoting qualities, including in the sphere of cardiovascular disease. Historically, the benefits have been linked to their well-recognised powerful antioxidant activity. However, the concept that the beneficial effects are attributable to direct antioxidant activity in vivo does not pay sufficient heed to the fact that polyphenols degrade rapidly, are poorly absorbed and rapidly metabolised, resulting in very low bioavailability. This review explores alternative mechanisms by which polyphenols, or their metabolites, exert biological activity via mechanisms that can be activated by physiologically relevant concentrations...
January 10, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28071611/microsomal-epoxide-hydrolase-gene-polymorphisms-and-susceptibility-to-prostate-cancer-a-systematic-review
#15
REVIEW
Dsl Srivastava
Microsomal epoxide hydrolase (mEH) is a crucial biotransformation enzyme that has capability to metabolize a large number of structurally divergent, highly reactive epoxides, and numerous environmentally exposed carcinogens. It catalyzes the conversion of xenobiotic epoxide compounds into more polar diol metabolites and may play important part of the enzymatic defense against adverse effects of foreign compounds. Most commonly, two functional polymorphisms affecting mEH enzyme activity have been identified: One in exon 3 and other in exon 4 of the mEH gene, which results in His113Tyr and Arg139His amino acid substitutions, respectively...
April 2016: Indian Journal of Cancer
https://www.readbyqxmd.com/read/28070106/excessive-activation-of-ahr-signaling-disrupts-neuronal-migration-in-the-hippocampal-ca1-region-in-the-developing-mouse
#16
Eiki Kimura, Ken-Ichiro Kubo, Toshihiro Endo, Kazunori Nakajima, Masaki Kakeyama, Chiharu Tohyama
The aryl hydrocarbon receptor (AhR) avidly binds dioxin, a ubiquitous environmental contaminant. Disruption of downstream AhR signaling has been reported to alter neuronal development, and rodent offspring exposed to dioxin during gestation and lactation showed abnormalities in learning and memory, emotion, and social behavior. However, the mechanism behind the disrupted AhR signaling and developmental neurotoxicity induced by xenobiotic ligands remains elusive. Therefore, we studied how excessive AhR activation affects neuronal migration in the hippocampal CA1 region of the developing mouse brain...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28067647/decomposition-of-xenobiotics-during-visible-light-irradiation-in-the-presence-of-immobilised-photosensitisers-kinetics-study
#17
M Olak-Kucharczyk, M Foszpańczyk, M Gmurek, S Ledakowicz
The objective of this work was to study the photosensitised oxidation of the xenobiotics benzylparaben (BeP) and 2,4dichlorophenol (2,4DCP) in aqueous solutions using photosensitisers immobilised into chitosan carrier particles and visible light radiation. Zn(II) phthalocyanine tetrasulfonate tetrasodium salt and Al(III) phthalocyanine chloride tetrasulfonic acid were used as photosensitisers. The major role of the singlet oxygen during photodegradation was proven by using scavengers of reactive oxygen species...
January 2017: Water Science and Technology: a Journal of the International Association on Water Pollution Research
https://www.readbyqxmd.com/read/28066829/the-multifaceted-role-of-nrf2-in-mitochondrial-function
#18
REVIEW
Kira M Holmström, Rumen V Kostov, Albena T Dinkova-Kostova
The transcription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2) is the master regulator of the cellular redox homeostasis. Nrf2 target genes comprise of a large network of antioxidant enzymes, proteins involved in xenobiotic detoxification, repair and removal of damaged proteins, inhibition of inflammation, as well as other transcription factors. In recent years it has emerged that as part of its role as a regulator of cytoprotective gene expression, Nrf2 impacts mitochondrial function. Increased Nrf2 activity defends against mitochondrial toxins...
December 2016: Curr Opin Toxicol
https://www.readbyqxmd.com/read/28065570/conservative-tracer-bromide-inhibits-pesticide-mineralisation-in-soil
#19
Tina B Bech, Annette E Rosenbom, Sebastian R Sørensen, Carsten S Jacobsen
Bromide is a conservative tracer that is often applied with non-conservative solutes such as pesticides to estimate their retardation in the soil. It has been applied in concentrations of up to 250 g Br L(-1), levels at which the growth of single-celled organisms can be inhibited. Bromide applications may therefore affect the biodegradation of non-conservative solutes in soil. The present study investigated the effect of potassium bromide (KBr) on the mineralisation of three pesticides - glyphosate, MCPA and metribuzin - in four agricultural A-horizon soils...
January 5, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28062095/the-liver-transcriptome-of-suckermouth-armoured-catfish-pterygoplichthys-anisitsi-loricariidae-identification-of-expansions-in-defensome-gene-families
#20
Thiago E Parente, Daniel A Moreira, Maithê G P Magalhães, Paula C C de Andrade, Carolina Furtado, Brian J Haas, John J Stegeman, Mark E Hahn
Pterygoplichthys is a genus of related suckermouth armoured catfishes native to South America, which have invaded tropical and subtropical regions worldwide. Physiological features, including an augmented resistance to organic xenobiotics, may have aided their settlement in foreign habitats. The liver transcriptome of Pterygoplichthys anisitsi was sequenced and used to characterize the diversity of mRNAs potentially involved in the responses to natural and anthropogenic chemicals. In total, 66,642 transcripts were assembled...
January 3, 2017: Marine Pollution Bulletin
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