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https://www.readbyqxmd.com/read/28529740/copy-number-variation-and-protein-expression-of-dot1l-in-pancreatic-adenocarcinoma-as-a-potential-drug-target
#1
Heike Loeser, Dirk Waldschmidt, Fabian Kuetting, Carina Heydt, Thomas Zander, Patrick Plum, Hakan Alakus, Reinhard Buettner, Alexander Quaas
Adenocarcinoma of the pancreas has a poor prognosis. At present, no relevant personalized targets have been identified. Sequencing studies have implicated gene alterations of disruptor of telomeric silencing 1 like histone lysine methyltransferase (DOT1L) in pancreatic adenocarcinoma. DOT1L is part of the histone modification system and catalyzes methylation of H3K79, which is crucial in cell signaling and DNA damage repair. DOT1L is considered to be a target of therapy in mixed lineage leukemia gene-deficient leukemia cases and a potential target in breast carcinoma...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28528485/lead-and-arsenic-accumulation-and-its-effects-on-plasma-cortisol-levels-in-oreochromis-sp
#2
Nguyen Quoc Thang, Bui The Huy, Le Van Tan, Nguyen Thi Kim Phuong
The accumulation, elimination and effect of heavy metals on plasma cortisol levels in Oreochromis sp. were studied in the exposure and recovery phases. In the exposure phase, the mean rate of accumulation in the tissues was in the order gill > liver > muscle for Pb exposure and muscle > liver > gill for As exposure. In the recovery phase, the order of elimination in the tissues was gill > liver > muscle for Pb and liver > gill > muscle for As. The amount of cortisol secreted by the Oreochromis sp...
May 20, 2017: Bulletin of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/28528315/bisphenol-a-and-replacements-in-thermal-paper-a-review
#3
REVIEW
Maria K Björnsdotter, Jacob de Boer, Ana Ballesteros-Gómez
Thermal paper contains potentially toxic compounds such as bisphenol A (BPA), which is used as a color developer. BPA has been reported in thermal paper in concentrations up to 42,600 μg g(-1). The exposure to BPA via dermal transfer has been recently discussed as a significant contribution to the overall human exposure and the estimated daily intake (EDI) has been reported up to 218 μg d(-1). BPA has been also detected in recycled paper with concentrations up to 46 μg g(-1). Due to the fact that BPA is a known endocrine disruptor and migrates from materials, regulatory restrictions have been established to prevent risks for the human health...
May 15, 2017: Chemosphere
https://www.readbyqxmd.com/read/28527034/simultaneous-determination-of-selected-hormones-endocrine-disruptor-compounds-and-pesticides-in-water-medium-at-trace-levels-by-gc-ms-after-dispersive-liquid-liquid-microextraction
#4
Dotse Selali Chormey, Çağdaş Büyükpınar, Fatma Turak, Okan Tarık Komesli, Sezgin Bakırdere
The need to enhance food safety has led to major advancements in pesticide productions, and though many benefits have been gained, environmental contamination has also risen from these chemicals that tend to persist in the environment. Some pesticides, together with other chemicals commonly called endocrine disruptor compounds, block the receptor sites of hormones or mimic displaced hormones, leading to imbalanced hormonal levels that result in health disorders and diseases. These chemicals occur at trace levels and are not directly detected by conventional analytical methods...
June 2017: Environmental Monitoring and Assessment
https://www.readbyqxmd.com/read/28525735/structure-based-rational-design-of-self-inhibitory-peptides-to-disrupt-the-intermolecular-interaction-between-the-troponin-subunits-c-and-i-in-neuropathic-pain
#5
Junmin Yu, Shilei Wang, Junjie Yu, Chuansheng Liu, Fenghe Xu, Shijie Wang, Yusheng Yi, Yanwei Yin
The troponin (Tn) is a ternary complex consisting of three subunits TnC, TnI and TnT; molecular disruption of the Tn complex has been recognized as an attractive strategy against neuropathic pain. Here, a self-inhibitory peptide is stripped from the switch region of TnI interaction interface with TnC, which is considered as a lead molecular entity and then used to generate potential peptide disruptors of TnC-TnI interaction based on a rational molecular design protocol. The region is a helical peptide segment capped by N- and C-terminal disorders...
May 3, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28521532/new-antivirals-for-the-treatment-of-chronic-hepatitis-b
#6
Vincent Soriano, Pablo Barreiro, Laura Benitez, Jose M Peña, Carmen de Mendoza
Current treatment with oral nucleos(t)ides entecavir or tenofovir provide sustained suppression of HBV replication and clinical benefit in most chronic hepatitis B virus (HBV) infected persons. However, HBV rebound generally occurs upon drug discontinuation due to persistence of genomic HBV reservoirs as episomic cccDNA and chromosomic integrated HBV-DNA. There is renewed enthusiasm on HBV drug discovery following recent successes with antivirals for hepatitis C and immunotherapies for some cancers. Areas covered: New drugs that target distinct steps of the HBV life cycle are been developed, including inhibitors of viral entry, new polymerase inhibitors, capsid and assembly inhibitors, virus release blockers, and disruptors of cccDNA formation and transcription...
May 18, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28521190/simultaneous-determination-of-bisphenol-a-and-estrogens-in-hair-samples-by-liquid-chromatography-electrospray-tandem-mass-spectrometry
#7
Chaelin Lee, Chong Hyeak Kim, Sunghwan Kim, Sung-Hee Cho
Bisphenol A (BPA), an endocrine disrupter, is widely used to make chemicals for polycarbonate, plastics, beverage containers, epoxy resins, and cash register receipts. BPA is one of the known xenoestrogens, which have weak estrogenic activity and cause obesity, diabetes, breast cancer, and reproductive disorders. Even though the concentration level of metabolomes in hair is usually lower than that in urine and blood, there are several reasons why we chose to use hair samples. First, the sampling procedure of hairs is simple...
May 11, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28521160/evidence-for-bisphenol-a-induced-disruption-of-maternal-thyroid-homeostasis-in-the-pregnant-ewe-at-low-level-representative-of-human-exposure
#8
Davy Guignard, Véronique Gayrard, Marlène Z Lacroix, Sylvie Puel, Nicole Picard-Hagen, Catherine Viguié
Many uncertainties remain regarding the potential of bisphenol A (BPA) as a thyroid disruptor in mammals and the relevance of experimental data to humans. The relevance of the exposure schemes used in experimental in vivo studies is also a major source of uncertainty when analysing the risk of BPA exposure for human health. In this context, the goals of our study, conducted in an ovine model relevant to human gestation and thyroid physiologies, were to: 1) determine the equivalence of subcutaneous and dietary exposures and 2) determine if environmentally relevant doses of BPA can alter gestational and newborn thyroid functions...
May 5, 2017: Chemosphere
https://www.readbyqxmd.com/read/28516783/antidiabetic-disruptors-of-the-glucokinase-glucokinase-regulatory-protein-complex-reorganize-a-coulombic-interface
#9
Juliana Martinez, Qing Xiao, Armen Zakarian, Brian G Miller
The glucokinase regulatory protein (GKRP) plays an essential role in glucose homeostasis by acting as a competitive inhibitor of glucokinase (GCK) and triggering its localization to the hepatocyte nucleus upon glucose deprivation. Metabolites such as fructose 6-phosphate and sorbitol 6-phosphate promote assembly of the GCK-GKRP complex, whereas fructose 1-phosphate and functionalized piperazines with potent in vivo antidiabetic activity disrupt the complex. Here, we establish the molecular basis by which these natural and synthetic ligands modulate the GCK-GKRP interaction...
May 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28516762/organophosphorus-flame-retardants-in-pregnant-women-and-their-transfer-to-chorionic-villi
#10
Fanrong Zhao, Mo Chen, Fumei Gao, Huan Shen, Jianying Hu
The potential for prenatal exposure has recently raised concerns over the health risks of endocrine disruptors; however, knowledge about human prenatal exposure to organophosphorus flame retardants (OPFRs) is lacking. In this study, 2-ethylhexyl diphenyl phosphate (EHDPP), tributyl phosphate (TBP), triphenyl phosphate (TPHP), and tris(2-chloroethyl) phosphate (TCEP) were detected in the majority of chorionic villus samples, with median concentrations of 13.6, 18.8, 11.1, and 0.51 ng/g dry weight (dw), respectively, significantly higher than those in the matching maternal decidua samples (5...
May 18, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28506834/safety-evaluation-of-dermal-exposure-to-phthalates-metabolism-dependent-percutaneous-absorption
#11
Masahiro Sugino, Tomomi Hatanaka, Hiroaki Todo, Yuko Mashimo, Takamasa Suzuki, Miho Kobayashi, Osamu Hosoya, Hideto Jinno, Kazuhiko Juni, Kenji Sugibayashi
Phthalates, known as reproductive toxicants and endocrine disruptors, are widely used as plasticizers in polyvinyl chloride products. The present study was conducted for risk identification of dermal exposure to phthalates. When dibutyl phthalate was applied to the skin of hairless rats and humans, only monobutyl phthalate appeared through the skin, and the permeability of the skin was higher than that after the application of the monoester directly. The inhibition of skin esterases made the skin impermeable to the metabolite following dermal exposure to dibutyl ester, whereas removal of the stratum corneum from the skin did not change the skin permeation behavior...
May 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28502861/analysis-of-testosterone-fatty-acid-esters-in-the-digestive-gland-of-mussels-by-liquid-chromatography-high-resolution-mass-spectrometry
#12
Cesare Guercia, Piergiorgio Cianciullo, Cinta Porte
Several studies have indicated that up to 70% of the total steroids detected in molluscs are in the esterified form and that pollutants, by modifying the esterification of steroids with fatty acids, might act as endocrine disrupters. However, despite the strong physiological significance of this process, there is almost no information on which fatty acids form the steroid esters and how this process is modulated. This study (a) investigates the formation of fatty acid esters of testosterone in digestive gland microsomal fractions of the mussel Mytilus galloprovincialis incubated with either palmitoly-CoA or CoA and ATP, and (b) assesses whether the endocrine disruptor tributyltin (TBT) interferes with the esterification of testosterone...
May 11, 2017: Steroids
https://www.readbyqxmd.com/read/28502780/biodegradation-of-endocrine-disruptors-in-urban-wastewater-using-pleurotus-ostreatus-bioreactor
#13
Zdena Křesinová, Lucie Linhartová, Alena Filipová, Martin Ezechiáš, Pavel Mašín, Tomáš Cajthaml
The white rot fungus Pleurotus ostreatus HK 35, which is also an edible industrial mushroom commonly cultivated in farms, was tested in the degradation of typical representatives of endocrine disrupters (EDCs; bisphenol A, estrone, 17β-estradiol, estriol, 17α-ethinylestradiol, triclosan and 4-n-nonylphenol); its degradation efficiency under model laboratory conditions was greater than 90% within 12 days and better than that of another published strain P. ostreatus 3004. A spent mushroom substrate from a local farm was tested for its applicability in various batch and trickle-bed reactors in degrading EDCs in model fortified and real communal wastewater...
May 11, 2017: New Biotechnology
https://www.readbyqxmd.com/read/28500084/bisphenol-a-promotes-hepatic-lipid-deposition-involving-kupffer-cell-m1-polarization-in-male-mice
#14
Qiong Lv, Rufei Gao, Chuan Peng, Juan Yi, Lulu Liu, Shumin Yang, Danting Li, Jinbo Hu, Ting Luo, Mei Mei, Ying Song, Chaodong Wu, Xiaoqiu Xiao, Qifu Li
Bisphenol A (BPA), as one of the most common environmental endocrine disruptors, is considered to promote hepatic lipid deposition, but the mechanisms has not been fully elucidated. The polarization of Kupffer cells (KCs) plays an important role in hepatic inflammation by promoting pro-inflammatory M1 phenotype (M1KCs), which contributes to dysregulated lipid metabolism. The purpose of this study is to investigate the role of KC polarization in BPA-induced hepatosteatosis in male mice. In this study, we examined hepatic lipid contents and quantified M1KC in BPA-treated CD1 mice, and further explored the interaction between KCs and hepatocytes by using conditional HepG2 cell culture...
May 12, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28496034/effect-of-perinatal-exposure-to-bisphenol-a-on-dna-methylation-and-histone-acetylation-in-cerebral-cortex-and-hippocampus-of-postnatal-male-mice
#15
Dhiraj Kumar, Mahendra Kumar Thakur
Bisphenol-A (BPA) is an estrogenic endocrine disruptor mostly used for the production of polycarbonate plastics and epoxy resins. Recently we have reported that perinatal BPA exposure impaired spatial memory through upregulation of synaptic proteins Neurexin1 and Neuroligin3 in male mice. As epigenetic mechanism is a key regulator of memory, we hypothesized that BPA might influence memory through epigenetic regulation of gene expression. Here we provide evidence that perinatal exposure to BPA decreased 5-mC DNA but increased histone H3 acetylation in cerebral cortex and hippocampus of postnatal 3 and 8 weeks male mice...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28486100/using-epigenetic-reprogramming-to-treat-pediatric-brain-cancer
#16
Milan G Chheda, David H Gutmann
In this issue of Cancer Cell, Nagaraja et al. dissect the molecular mechanisms underlying therapeutic responses to transcriptional disruptors in the fatal pediatric brain tumor, diffuse intrinsic pontine glioma (DIPG). Moreover, they identify super-enhancers mediating these effects, highlighting how normal brain developmental programs can be hijacked in cancer.
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28482793/computational-screening-and-design-for-compounds-that-disrupt-protein-protein-interactions
#17
David K Johnson, John Karanicolas
Protein-protein interactions play key roles in all biological processes, motivating numerous campaigns to seek small-molecule disruptors of therapeutically relevant interactions. Two decades ago, the prospect of developing small-molecule inhibitors was thought to be perhaps impossible due to the potentially undruggable nature of the protein surfaces involved; this viewpoint was reinforced by the limited successes provided from traditional high-throughput screens. To date, however, refinement of new experimental approaches has led to a multitude of inhibitors against many different targets...
May 8, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28479067/enhanced-metabolite-annotation-via-dynamic-retention-time-prediction-steroidogenesis-alterations-as-a-case-study
#18
Giuseppe Marco Randazzo, David Tonoli, Petra Strajhar, Ioannis Xenarios, Alex Odermatt, Julien Boccard, Serge Rudaz
The development of metabolomics based on ultra-high pressure liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) now allows hundreds to thousands of metabolites to be simultaneously monitored in biological matrices. In that context, bioinformatics and multivariate data analysis (MVA) play a crucial role in the detection of relevant alteration patterns. However, sound biological interpretations must necessarily be supported by metabolite identifications to be definitive or at least have a high degree of confidence...
April 23, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28474816/the-rise-of-glyphosate-and-new-opportunities-for-biosentinel-early-warning-studies
#19
Zoe Kissane, Jill M Shephard
Glyphosate has become the most commonly used herbicide worldwide, with a reputation of being environmentally benign, non-toxic and safe to wildlife and humans. However, studies have indicated its toxicity has been underestimated, and that its persistence in the environment is greater than once thought. Its actions as a neurotoxin and endocrine disruptor indicate its potential to act in similar ways to persistent organic pollutants (POPs) such as the organochlorine (OC) chemicals dichlorodiphenyltrichloroethane (DDT) and dioxin...
May 5, 2017: Conservation Biology: the Journal of the Society for Conservation Biology
https://www.readbyqxmd.com/read/28474689/endocrine-disruptors-pfass-sex-hormones-and-asthma
#20
Claire Greenhill
No abstract text is available yet for this article.
May 5, 2017: Nature Reviews. Endocrinology
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