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https://www.readbyqxmd.com/read/28821762/multi-tissue-interactions-in-an-integrated-three-tissue-organ-on-a-chip-platform
#1
Aleksander Skardal, Sean V Murphy, Mahesh Devarasetty, Ivy Mead, Hyun-Wook Kang, Young-Joon Seol, Yu Shrike Zhang, Su-Ryon Shin, Liang Zhao, Julio Aleman, Adam R Hall, Thomas D Shupe, Andre Kleensang, Mehmet R Dokmeci, Sang Jin Lee, John D Jackson, James J Yoo, Thomas Hartung, Ali Khademhosseini, Shay Soker, Colin E Bishop, Anthony Atala
Many drugs have progressed through preclinical and clinical trials and have been available - for years in some cases - before being recalled by the FDA for unanticipated toxicity in humans. One reason for such poor translation from drug candidate to successful use is a lack of model systems that accurately recapitulate normal tissue function of human organs and their response to drug compounds. Moreover, tissues in the body do not exist in isolation, but reside in a highly integrated and dynamically interactive environment, in which actions in one tissue can affect other downstream tissues...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820500/odorous-compounds-from-poultry-manure-induce-dna-damage-nuclear-changes-and-decrease-cell-membrane-integrity-in-chicken-liver-hepatocellular-carcinoma-cells
#2
Adriana Nowak, Tadeusz Bakuła, Katarzyna Matusiak, Remigiusz Gałęcki, Sebastian Borowski, Beata Gutarowska
Animal breeding and management of organic wastes pose a serious problem to the health of livestock and workers, as well as the nearby residents. The aim of the present study was to determine the mechanisms of toxicity of selected common odorous compounds from poultry manure, including ammonia, dimethylamine (DMA), trimethylamine (TMA), butyric acid, phenol, and indole. We measured their genotoxic and cytotoxic activity in the model chicken cell line (LMH), in vitro, by comet assay and lactate dehydrogenase assay, respectively...
August 18, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28820390/small-molecule-inhibitors-of-dna-pk-for-tumor-sensitization-to-anticancer-therapy
#3
M Pospisilova, M Seifrtova, M Rezacova
The most sensitive cell structure - a DNA molecule, is the common target of cancer therapy. DNA damage response (controlled by enzymes from the phosphatidylinositol 3-kinase-related kinases family - PIKK) presents many encouraging targets for improving both conventional cytotoxic anticancer therapy and individualized monotherapy. DNA-dependent protein kinase (DNA-PK) is a member of the PIKK superfamily and plays an important role in the detection and repair of DNA double-strand breaks via the non-homologous end-joining pathway...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28819233/biology-physiology-and-gene-expression-of-grasshopper-oedaleus-asiaticus-exposed-to-diet-stress-from-plant-secondary-compounds
#4
Xunbing Huang, Jingchuan Ma, Xinghu Qin, Xiongbing Tu, Guangchun Cao, Guangjun Wang, Xiangqun Nong, Zehua Zhang
We studied the role of plant primary and secondary metabolites in mediating plant-insect interactions by conducting a no-choice single-plant species field experiment to compare the suitability, enzyme activities, and gene expression of Oedaleus asiaticus grasshoppers feeding on four host and non-host plants with different chemical traits. O. asiaticus growth showed a positive relationship to food nutrition content and a negative relationship to secondary compounds content. Grasshopper amylase, chymotrypsin, and lipase activities were positively related to food starch, crude protein, and lipid content, respectively...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28815320/inhibitory-growth-evaluation-and-apoptosis-induction-in-mcf-7-cancer-cells-by-new-5-aryl-2-butylthio-1-3-4-oxadiazole-derivatives
#5
Rashmin Khanam, Kamal Ahmad, Iram I Hejazi, Ibrar A Siddique, Vikash Kumar, Abdul Roouf Bhat, Amir Azam, Fareeda Athar
BACKGROUND: Cancer has become one of the global health issues and it is the life-threatening disease characterized by unrestrained growth of cells. Despite various advances being adopted by chemotherapeutic management, the use of the current anticancer drugs such as Doxorubicin, Asparginase, Methotrexate, Vincristine remains limited due to high toxicity, side effects and developing drug resistance. Apoptosis is a crucial cellular process and improper regulation of apoptotic signaling pathways may lead to cancer formation...
August 16, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28814164/cpx-351-in-acute-myeloid-leukemia-can-a-new-formulation-maximize-the-efficacy-of-old-compounds
#6
Claudia Brunetti, Luisa Anelli, Antonella Zagaria, Giorgina Specchia, Francesco Albano
The management of Acute Myeloid Leukemia (AML) (with the exception of acute promyelocytic leukemia) has remained largely unchanged over the past 40 years. In particular, patients defined as high-risk, according to the 2017 European Leukemia Net recommendations, represent a subgroup with poor response to current therapies that are frequently associated with high-grade toxicity and potentially fatal complications. Areas covered: Preliminary results from an ongoing phase III clinical trial suggest that CPX-351 could represent an interesting treatment option in both induction and "bridge-to-transplant" settings...
August 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28812956/toxicity-identification-and-evaluation-for-the-effluent-from-a-nonmetallic-mineral-mining-facility-in-korea-using-d-magna
#7
Sungjong Lee, Hongjoo Ha, JinKyung Hong, Guyoung Kang, Chunsang Hong
Industrial wastewater has attracted increasing attention in recent years because of its impact on ecosystems and human health. Whole-effluent tests are generally used to monitor toxicities of unknown chemicals and conventional pollutants from industrial effluent discharges. This study described identification evaluation (TIE) procedures to determine the acute toxicity of a nonmetallic mineral mining facility effluent that was toxic to Daphnia magna. In the characterization step (TIE phase I), toxic effects of heavy metals, organic compounds, oxidants, volatile organic compounds, suspended solids, and ammonia were screened...
January 1, 2017: Toxicology and Industrial Health
https://www.readbyqxmd.com/read/28811165/dicyanomethylene-substituted-benzothiazole-squaraines-the-efficiency-of-photodynamic-therapy-in-vitro-and-in-vivo
#8
Yongbiao Wei, Xiaoxiao Hu, Luyao Shen, Bing Jin, Xiangjun Liu, Weihong Tan, Dihua Shangguan
The lack of ideal photosensitizers limits the clinicalapplication of photodynamic therapy (PDT). Here we report the PDT efficiency of dicyanomethylene substituted benzothiazole squaraine derivatives. This class of squaraine derivatives possess strong absorption and long excitation and emission wavelengths (ex/em, 685/720nm). They show negligible dark toxicity, but can generate singlet oxygen under irradiation resulting in the apoptosis and necrosis of cells (phototoxicity). Changing the side chains of these compounds greatly influences their albumin-binding rate, cellular uptake and their phototoxicity...
August 9, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28810231/cr-induced-cellular-injury-and-necrosis-in-glycine-max-l-biochemical-mechanism-of-oxidative-damage-in-chloroplast
#9
Kalimuthu Balasaraswathi, Sivalingam Jayaveni, Janardhanam Sridevi, Dhanasingh Sujatha, Kavati Phebe Aaron, Chellan Rose
Chromium-induced toxicity and mechanisms of cell death involved in plants are yet to be fully elucidated. To understand the events of these processes, the stress response of the soybean plant using trivalent and hexavalent chromium compounds, namely, basic chromium sulphate (BCS) and potassium dichromate (K2Cr2O7) was investigated. The leaf surface morphology for stomatal aperture, wax deposition and presence of trichomes for chromium accumulation was examined by SEM-EDAX and light microscopy. The leaf mesophyll cell integrity was identified by trypan blue staining; chlorophyll autofluorescence, ROS generation and mitochondrial function were studied by fluorescence microscopy using different dyes...
August 2, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28810189/hydroxy-substituted-trans-cinnamoyl-derivatives-as-multifunctional-tools-in-the-context-of-alzheimer-s-disease
#10
Angela De Simone, Manuela Bartolini, Andrea Baschieri, Kim Y P Apperley, Huan Huan Chen, Melissa Guardigni, Serena Montanari, Tereza Kobrlova, Ondrej Soukup, Luca Valgimigli, Vincenza Andrisano, Jeffrey W Keillor, Manuela Basso, Andrea Milelli
Alzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. In recent years, a plethora of proteins and biochemical pathways has been proposed as possible targets to counteract neurotoxicity. Although the complex scenario is not completely elucidated, close relationships are emerging among some of these actors. In particular, increasing evidence has shown that aggregation of amyloid beta (Aβ), glycogen synthase kinase 3β (GSK-3β) and oxidative stress are strictly interconnected and their concomitant modulation may have a positive and synergic effect in contrasting AD-related impairments...
July 25, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28808378/rutamarin-an-active-constituent-from-ruta-angustifolia-pers-induced-apoptotic-cell-death-in-the-ht29-colon-adenocarcinoma-cell-line
#11
Shafinah Ahmad Suhaimi, Sok Lai Hong, Sri Nurestri Abdul Malek
BACKGROUND: Ruta angustifolia Pers. is a perennial herb that is cultivated worldwide, including Southeast Asia, for the treatment of various diseases as traditional medicine. OBJECTIVE: The purpose of the study was to identify an active principle of R. angustifolia and to investigate its effect on the HT29 cell death. MATERIALS AND METHODS: The methanol and fractionated extracts (hexane, chloroform, ethyl acetate, and water) of R. angustifolia Pers...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28806568/a-simple-high-performance-liquid-chromatography-mass-spectrometry-method-for-therapeutic-drug-monitoring-of-isavuconazole-and-four-other-antifungal-drugs-in-human-plasma-samples
#12
Giovanna Fatiguso, Fabio Favata, Ilaria Zedda, Amedeo De Nicolò, Jessica Cusato, Valeria Avataneo, Giovanni Di Perri, Antonio D'Avolio
Triazoles chanced the prevention and treatment of invasive fungal infections, but their pharmacokinetic properties are still unclear. In particular, isavuconazole (ISC) is a new broad-spectrum antifungal triazole approved in 2015 as first-line treatment for intravenous and oral use against invasive aspergillosis and for mucormycosis. Nowadays, the optimal management of the treatments with triazoles requires the use of Therapeutic Drug Monitoring (TDM), in order to prevent sub-therapeutic or toxic concentrations...
August 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28804711/annotation-of-the-nuclear-receptors-in-an-estuarine-fish-species-fundulus-heteroclitus
#13
William S Baldwin, W Tyler Boswell, Gautam Ginjupalli, Elizabeth J Litoff
The nuclear receptors (NRs) are ligand-dependent transcription factors that respond to various internal as well as external cues such as nutrients, pheromones, and steroid hormones that play crucial roles in regulation and maintenance of homeostasis and orchestrating the physiological and stress responses of an organism. We annotated the Fundulus heteroclitus (mummichog; Atlantic killifish) nuclear receptors. Mummichog are a non-migratory, estuarine fish with a limited home range often used in environmental research as a field model for studying ecological and evolutionary responses to variable environmental conditions such as salinity, oxygen, temperature, pH, and toxic compounds because of their hardiness...
2017: Nuclear Receptor Research
https://www.readbyqxmd.com/read/28803990/high-doses-of-baicalin-induces-kidney-injury-and-fibrosis-through-regulating-tgf-%C3%AE-smad-signaling-pathway
#14
Yi Cai, Wanqing Ma, Yichuan Xiao, Bo Wu, Xiaobing Li, Fengrong Liu, Jianhua Qiu, Genshui Zhang
Baicalin is a major flavonoid compound purified from Scutellariae radix, which has been described as an herb in the Chinese Pharmacopoeia. Previous studies have suggested baicalin possessed extensive anti-inflammatory, anti-cancer, anti-viral properties. However, up to known, there have been no reports of safety and toxicity in the rats following oral administration of baicalin. In this present study, we showed the first evidence that treatment of baicalin (400, 800 and 1600mg/kg/day) induced significantly kidney injury and fibrosis...
August 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28803761/an-in-silico-perspective-on-the-toxicodynamic-of-tetrodotoxin-and-analogues-a-tool-for-supporting-the-hazard-identification
#15
Luca Dellafiora, Gianni Galaverna, Chiara Dall'Asta
Tetrodotoxin (TTX) is a potent neurotoxin naturally found in terrestrial and marine animals targeting the voltage-gated sodium channels. Historically, TTX has raised food safety concerns mainly in the Asian countries due to the consumption of the typical pufferfish-derived delicacy fugu. However, the diffusion of TTX is getting wider today, reasonably threating in a close future a broader number of consumers than before. The understanding of TTX group toxicity is still incomplete as most of the analogues and metabolites found together with TTX are largely understudied...
August 10, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28803722/advantages-of-analyzing-postmortem-brain-samples-in-routine-forensic-drug-screening-case-series-of-three-non-natural-deaths-tested-positive-for-lysergic-acid-diethylamide-lsd
#16
Marie Mardal, Sys Stybe Johansen, Ragnar Thomsen, Kristian Linnet
Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma and urine when available. LSD, its main metabolite 2-oxo-3-hydroxy-LSD (oxo-HO-LSD), and iso-LSD were quantified in biological samples according to a previously published procedure involving liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)...
July 30, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28803438/inhibitor-of-endocannabinoid-deactivation-protects-against-in-vitro-and-in-vivo-neurotoxic-effects-of-paraoxon
#17
Karen L G Farizatto, Sara A McEwan, Vinogran Naidoo, Spyros P Nikas, Vidyanand G Shukla, Michael F Almeida, Aaron Byrd, Heather Romine, David A Karanian, Alexandros Makriyannis, Ben A Bahr
The anticholinesterase paraoxon (Pxn) is related to military nerve agents that increase acetylcholine levels, trigger seizures, and cause excitotoxic damage in the brain. In rat hippocampal slice cultures, high-dose Pxn was applied resulting in a presynaptic vulnerability evidenced by a 64% reduction in synapsin IIb (syn IIb) levels, whereas the postsynaptic protein GluR1 was unchanged. Other signs of Pxn-induced cytotoxicity include the oxidative stress-related production of stable 4-hydroxynonenal (4-HNE)-protein adducts...
August 12, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28803044/new-racemic-annulated-pyrazolo-1-2-b-phthalazines-as-tacrine-like-ache-inhibitors-with-potential-use-in-alzheimer-s-disease
#18
Leili Jalili-Baleh, Hamid Nadri, Alireza Moradi, Syed Nasir Abbas Bukhari, Mojtaba Shakibaie, Mandana Jafari, Mostafa Golshani, Farshad Homayouni Moghadam, Loghman Firoozpour, Ali Asadipour, Saeed Emami, Mehdi Khoobi, Alireza Foroumadi
A novel series of tacrine-like compounds 7a-u possessing a fused pyrazolo[1,2-b]phthalazine structure were designed and synthesized as potent and selective inhibitors of AChE. The in-vitro biological assessments demonstrated that several compounds had high anti-AChE activity at nano-molar level. The more promising compound 7l with IC50 of 49 nM was 7-fold more potent than tacrine and unlike tacrine, it was highly selective against AChE over BuChE. The cell-based assays against hepatocytes (HepG2) and neuronal cell line (PC12) revealed that 7l had significantly lower hepatotoxicity compared to tacrine, with additional neuroprotective activity against H2O2-induced damage in PC12 cells...
July 31, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28802893/complex-mixtures-of-dissolved-pesticides-show-potential-aquatic-toxicity-in-a-synoptic-study-of-midwestern-u-s-streams
#19
Lisa H Nowell, Patrick W Moran, Travis S Schmidt, Julia E Norman, Naomi Nakagaki, Megan E Shoda, Barbara J Mahler, Peter C Van Metre, Wesley W Stone, Mark W Sandstrom, Michelle L Hladik
Aquatic organisms in streams are exposed to pesticide mixtures that vary in composition over time in response to changes in flow conditions, pesticide inputs to the stream, and pesticide fate and degradation within the stream. To characterize mixtures of dissolved-phase pesticides and degradates in Midwestern streams, a synoptic study was conducted at 100 streams during May-August 2013. In weekly water samples, 94 pesticides and 89 degradates were detected, with a median of 25 compounds detected per sample and 54 detected per site...
August 4, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28800557/predicting-and-experimental-evaluating-bio-electrochemical-synthesis-a-case-study-with-clostridium-kluyveri
#20
Christin Koch, Anne Kuchenbuch, Frauke Kracke, Paul V Bernhardt, Jens Krömer, Falk Harnisch
Microbial electrosynthesis is a highly promising application of microbial electrochemical technologies for the sustainable production of organic compounds. At the same time a multitude of questions need to be answered and challenges to be met. Central for its further development is using appropriate electroactive microorganisms and their efficient extracellular electron transfer (EET) as well as wiring of the metabolism to EET. Among others, Clostridia are believed to represent electroactive microbes being highly promising for microbial electrosynthesis...
July 25, 2017: Bioelectrochemistry
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