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https://www.readbyqxmd.com/read/28968186/development-and-therapeutic-potential-of-small-molecule-modulators-of-circadian-systems
#1
Zheng Chen, Seung-Hee Yoo, Joseph S Takahashi
Circadian timekeeping systems drive oscillatory gene expression to regulate essential cellular and physiological processes. When the systems are perturbed, pathological consequences ensue and disease risks rise. A growing number of small-molecule modulators have been reported to target circadian systems. Such small molecules, identified via high-throughput screening or derivatized from known scaffolds, have shown promise as drug candidates to improve biological timing and physiological outputs in disease models...
October 2, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28934561/epigenetic-mechanisms-regulating-adaptive-responses-to-targeted-kinase-inhibitors-in-cancer
#2
Steven P Angus, Jon S Zawistowski, Gary L Johnson
Although targeted inhibition of oncogenic kinase drivers has achieved remarkable patient responses in many cancers, the development of resistance has remained a significant challenge. Numerous mechanisms have been identified, including the acquisition of gatekeeper mutations, activating pathway mutations, and copy number loss or gain of the driver or alternate nodes. These changes have prompted the development of kinase inhibitors with increased selectivity, use of second-line therapeutics to overcome primary resistance, and combination treatment to forestall resistance...
September 15, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28926760/laminin-%C3%AE-5-substrates-promote-survival-network-formation-and-functional-development-of-human-pluripotent-stem-cell-derived-neurons-in-vitro
#3
Anu Hyysalo, Mervi Ristola, Meeri E-L Mäkinen, Sergei Häyrynen, Matti Nykter, Susanna Narkilahti
Laminins are one of the major protein groups in the extracellular matrix (ECM) and specific laminin isoforms are crucial for neuronal functions in the central nervous system in vivo. In the present study, we compared recombinant human laminin isoforms (LN211, LN332, LN411, LN511, and LN521) and laminin isoform fragment (LN511-E8) in in vitro cultures of human pluripotent stem cell (hPSC)-derived neurons. We showed that laminin substrates containing the α5-chain are important for neuronal attachment, viability and network formation, as detected by phase contrast imaging, viability staining, and immunocytochemistry...
September 12, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28924347/the-mechanisms-of-graphene-based-materials-induced-programmed-cell-death-a-review-of-apoptosis-autophagy-and-programmed-necrosis
#4
REVIEW
Lingling Ou, Shaoqiang Lin, Bin Song, Jia Liu, Renfa Lai, Longquan Shao
Graphene-based materials (GBMs) are widely used in many fields, including biomedicine. To date, much attention had been paid to the potential unexpected toxic effects of GBMs. Here, we review the recent literature regarding the impact of GBMs on programmed cell death (PCD). Apoptosis, autophagy, and programmed necrosis are three major PCDs. Mechanistic studies demonstrated that the mitochondrial pathways and MAPKs (JNK, ERK, and p38)- and TGF-β-related signaling pathways are implicated in GBMs-induced apoptosis...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28915649/digoxin-induced-anemia-among-patients-with-atrial-fibrillation-and-heart-failure-clinical-data-analysis-and-drug-gene-interaction-network
#5
Yubi Lin, Siqi He, Ruiling Feng, Zhe Xu, Wanqun Chen, Zifeng Huang, Yang Liu, Qianhuan Zhang, Bin Zhang, Kejian Wang, Shulin Wu
Digoxin is widely used to treat various heart conditions. In order to clarify the association between digoxin and anemia adverse reaction, we inspected case reports submitted to the FDA Adverse Event Reporting System (FAERS) between January 2004 and December 2015. These reports involved 75618 atrial fibrillation patients and 15699 heart failure patients. Compared to other therapies, digoxin treatment was significantly more likely to be concurrent with anemia adverse reaction among both atrial fibrillation patients (pooled OR = 1...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903495/rna-seq-of-human-neural-progenitor-cells-exposed-to-lead-pb-reveals-transcriptome-dynamics-splicing-alterations-and-disease-risk-associations
#6
Peng Jiang, Zhonggang Hou, Jennifer M Bolin, James A Thomson, Ron Stewart
Lead (Pb) is a well-known toxicant, especially for the developing nervous system, albeit the mechanism is largely unknown. In this study, we use time series RNA-seq to conduct a genome-wide survey of the transcriptome response of human embryonic stem cell-derived neural progenitor cells to lead treatment. Using a dynamic time warping algorithm coupled with statistical tests, we find that lead can either accelerate or decelerate the expression of specific genes during the time series. We further show that lead disrupts a neuron- and brain-specific splicing factor NOVA1 regulated splicing network...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28903493/editor-s-highlight-formulation-and-toxicology-evaluation-of-the-intrathecal-ayx1-dna-decoy-in-sprague-dawley-rats
#7
Julien Mamet, David C Yeomans, Tony L Yaksh, Donald C Manning, Scott Harris
The longevity of pain after surgery is debilitating and limits the recovery of patients. AYX1 is a double-stranded, unprotected, 23 base-pair oligonucleotide designed to reduce acute post-surgical pain and prevent its chronification with a single intrathecal perioperative dose. AYX1 mimics the DNA sequence normally bound by EGR1 on chromosomes, a transcription factor transiently induced in the dorsal root ganglia-spinal cord network following a noxious input. AYX1 binds to EGR1 and prevents it from launching waves of gene regulation that are necessary to maintain pain over time...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28903485/editor-s-highlight-mechanistic-toxicity-tests-based-on-an-adverse-outcome-pathway-network-for-hepatic-steatosis
#8
Michelle M Angrish, Charlene A McQueen, Elaine Cohen-Hubal, Maribel Bruno, Yue Ge, Brian N Chorley
Risk assessors use liver endpoints in rodent toxicology studies to assess the safety of chemical exposures. Yet, rodent endpoints may not accurately reflect human responses. For this reason and others, human-based invitro models are being developed and anchored to adverse outcome pathways to better predict adverse human health outcomes. Here, a networked adverse outcome pathway-guided selection of biology-based assays for lipid uptake, lipid efflux, fatty acid oxidation, and lipid accumulation were developed...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28893249/assessment-of-the-potential-respiratory-hazard-of-volcanic-ash-from-future-icelandic-eruptions-a-study-of-archived-basaltic-to-rhyolitic-ash-samples
#9
David E Damby, Claire J Horwell, Gudrun Larsen, Thorvaldur Thordarson, Maura Tomatis, Bice Fubini, Ken Donaldson
BACKGROUND: The eruptions of Eyjafjallajökull (2010) and Grímsvötn (2011), Iceland, triggered immediate, international consideration of the respiratory health hazard of inhaling volcanic ash, and prompted the need to estimate the potential hazard posed by future eruptions of Iceland's volcanoes to Icelandic and Northern European populations. METHODS: A physicochemical characterization and toxicological assessment was conducted on a suite of archived ash samples spanning the spectrum of past eruptions (basaltic to rhyolitic magmatic composition) of Icelandic volcanoes following a protocol specifically designed by the International Volcanic Health Hazard Network...
September 11, 2017: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/28889265/manganese-and-the-insulin-igf-signaling-network-in-huntington-s-disease-and-other-neurodegenerative-disorders
#10
Miles R Bryan, Aaron B Bowman
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease resulting in motor impairment and death in patients. Recently, several studies have demonstrated insulin or insulin-like growth factor (IGF) treatment in models of HD, resulting in potent amelioration of HD phenotypes via modulation of the PI3K/AKT/mTOR pathways. Administration of IGF and insulin can rescue microtubule transport, metabolic function, and autophagy defects, resulting in clearance of Huntingtin (HTT) aggregates, restoration of mitochondrial function, amelioration of motor abnormalities, and enhanced survival...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28889247/guidelines-for-autopsy-investigation-of-sudden-cardiac-death-2017-update-from-the-association-for-european-cardiovascular-pathology
#11
Cristina Basso, Beatriz Aguilera, Jytte Banner, Stephan Cohle, Giulia d'Amati, Rosa Henriques de Gouveia, Cira di Gioia, Aurelie Fabre, Patrick J Gallagher, Ornella Leone, Joaquin Lucena, Lubov Mitrofanova, Pilar Molina, Sarah Parsons, Stefania Rizzo, Mary N Sheppard, Maria Paz Suárez Mier, S Kim Suvarna, Gaetano Thiene, Allard van der Wal, Aryan Vink, Katarzyna Michaud
Although sudden cardiac death (SCD) is one of the most important modes of death in Western countries, pathologists and public health physicians have not given this problem the attention it deserves. New methods of preventing potentially fatal arrhythmias have been developed and the accurate diagnosis of the causes of SCD is now of particular importance. Pathologists are responsible for determining the precise cause and mechanism of sudden death but there is still considerable variation in the way in which they approach this increasingly complex task...
September 9, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28812380/analysis-of-an-8-hour-acetylcysteine-infusion-protocol-for-repeated-supratherapeutic-ingestion-rsti-of-paracetamol
#12
Anselm Wong, Naren Gunja, Richard McNulty, Andis Graudins
OBJECTIVES: In Australia, the treatment guideline for patients with repeated supratherapeutic ingestion (RSTI) of paracetamol recommends an abbreviated acetylcysteine regimen if the paracetamol concentration is low (<10 mg/L) and alanine aminotransferase (ALT) is normal or static after 8 hours of infusion. There are currently no studies of this recommendation. METHOD: A retrospective review of paracetamol overdose presentations from October 2009 to August 2016 in two hospital toxicology networks was performed...
August 16, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28802948/modelling-the-toxicity-of-a-large-set-of-metal-and-metal-oxide-nanoparticles-using-the-ochem-platform
#13
Vasyl Kovalishyn, Natalia Abramenko, Iryna Kopernyk, Larysa Charochkina, Larysa Metelytsia, Igor V Tetko, Willie Peijnenburg, Leonid Kustov
Inorganic nanomaterials have become one of the new areas of modern knowledge and technology and have already found an increasing number of applications. However, some nanoparticles show toxicity to living organisms, and can potentially have a negative influence on environmental ecosystems. While toxicity can be determined experimentally, such studies are time consuming and costly. Computational toxicology can provide an alternative approach and there is a need to develop methods to reliably assess Quantitative Structure-Property Relationships for nanomaterials (nano-QSPRs)...
August 9, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28771645/opportunity-for-collaboration-between-radiation-injury-treatment-network-centers-and-medical-toxicology-specialists
#14
Elizabeth Davlantes, Samuel Shartar, Jennifer Venero, Alaina Steck, Amelia Langston, Ziad N Kazzi
OBJECTIVES: The Radiation Injury Treatment Network (RITN) comprises >50 centers across the United States that are poised to care for victims of a radiation emergency. The network is organized around bone marrow transplant centers because these facilities excel in both radiation medicine and the care of patients with severe bone marrow depression. A radiation emergency may cause not only irradiation from an external source but also internal contamination with radioactive material. Because medical toxicologists are trained in radiation injury management and have expertise in the management of internal contamination, RITN centers may benefit from partnerships with medical toxicology resources, which may be located at academic medical centers, hospital inpatient clinical services, outpatient clinics, or poison control centers...
August 2017: Southern Medical Journal
https://www.readbyqxmd.com/read/28771410/international-variability-in-gastrointestinal-decontamination-with-acute-poisonings
#15
MULTICENTER STUDY
Santiago Mintegi, Stuart R Dalziel, Beatriz Azkunaga, Javier Prego, Eunate Arana-Arri, Yordana Acedo, Lorea Martinez-Indart, Javier Benito, Nathan Kuppermann
BACKGROUND AND OBJECTIVES: Identifying international differences in the management of acute pediatric poisonings may help improve the quality of care. The objective of this study was to assess the international variation and appropriateness of gastrointestinal decontamination (GID) procedures performed in children and adolescents who present with acute poisonings to emergency departments. METHODS: This was an international, multicenter, cross-sectional prospective study including children <18 years with poisoning exposures presenting to 105 emergency departments in 20 countries from 8 global regions belonging to the Pediatric Emergency Research Networks...
August 2017: Pediatrics
https://www.readbyqxmd.com/read/28736676/label-free-photoacoustic-imaging-of-the-cardio-cerebrovascular-development-in-the-embryonic-zebrafish
#16
Qian Chen, Tian Jin, Weizhi Qi, Xianming Mo, Lei Xi
Zebrafish play an important role in biology, pharmacology, toxicology, and medicine. The cardio-cerebrovascular development of zebrafish is particularly critical to understand both brain disorders and cardiovascular diseases in human. In this paper, we applied optical resolution photoacoustic microscopy (ORPAM) to image the whole-body vasculature of the embryonic zebrafish with a special focus on the development of the cardio-cerebrovascular system. Using the intrinsic optical absorption contrast of the embryo, we successfully visualized the formation of the cardio-cerebrovascular network in high-resolution using a 10 × objective, and monitored the whole-body vascular development using a 4 × objective...
April 1, 2017: Biomedical Optics Express
https://www.readbyqxmd.com/read/28724094/temperature-impacts-on-soil-microbial-communities-and-potential-implications-for-the-biodegradation-of-turfgrass-pesticides
#17
Lisa M Reedich, Michael D Millican, Paul L Koch
Maintaining healthy turfgrass often results in the use of pesticides to manage weed, insect, and disease pests. To identify and understand potential nontarget impacts of pesticide usage while still maintaining attractive and functional turfgrass sites, it is important to improve our understanding of how pesticides degrade in various environments throughout the growing season. Temperature heavily influences microbial community composition and activity, and the microbial community often heavily influences pesticide degradation in soil ecosystems...
May 2017: Journal of Environmental Quality
https://www.readbyqxmd.com/read/28686651/a-preliminary-approach-to-quantifying-the-overall-environmental-risks-posed-by-development-projects-during-environmental-impact-assessment
#18
Sam Nicol, Iadine Chadès
Environmental impact assessment (EIA) is used globally to manage the impacts of development projects on the environment, so there is an imperative to demonstrate that it can effectively identify risky projects. However, despite the widespread use of quantitative predictive risk models in areas such as toxicology, ecosystem modelling and water quality, the use of predictive risk tools to assess the overall expected environmental impacts of major construction and development proposals is comparatively rare. A risk-based approach has many potential advantages, including improved prediction and attribution of cause and effect; sensitivity analysis; continual learning; and optimal resource allocation...
2017: PloS One
https://www.readbyqxmd.com/read/28679289/synthesis-of-%C3%AE-cyclodextrin-hydrogel-nanoparticles-for-improving-the-solubility-of-dexibuprofen-characterization-and-toxicity-evaluation
#19
Qandeel Khalid, Mahmood Ahmad, Muhammad Usman Minhas
OBJECTIVE: This study was aimed to enhance aqueous solubility of dexibuprofen through designing β-cyclodextrin (βCD) hydrogel nanoparticles and to evaluate toxicological potential through acute toxicity studies in rats. SIGNIFICANCE: Dexibuprofen is a non-steroidal analgesic and anti-inflammatory drug that is one of safest over the counter medications. However, its clinical effectiveness is hampered due to poor aqueous solubility. METHODS: βCD hydrogel nanoparticles were prepared and characterized by percent yield, drug loading, solubilization efficiency, FTIR, XRD, DSC, FESEM and in-vitro dissolution studies...
November 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28676675/hmgcs2-is-a-key-ketogenic-enzyme-potentially-involved-in-type-1-diabetes-with-high-cardiovascular-risk
#20
Sanket Kumar Shukla, Weijing Liu, Kunal Sikder, Sankar Addya, Amrita Sarkar, Yidong Wei, Khadija Rafiq
Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined. To learn more about biological pathways that are potentially involved in T1D with cardiac dysfunction, we sought to identify differentially expressed genes in the T1D heart. Our study used T1D mice with severe hyperglycemia along with significant deficits in echocardiographic measurements...
July 4, 2017: Scientific Reports
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