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https://www.readbyqxmd.com/read/28434146/differential-regulation-of-h3s10-phosphorylation-mitosis-progression-and-cell-fate-by-aurora-kinase-b-and-c-in-mouse-preimplantation-embryos
#1
Wenzhi Li, Peizhe Wang, Bingjie Zhang, Jing Zhang, Jia Ming, Wei Xie, Jie Na
Coordination of cell division and cell fate is crucial for the successful development of mammalian early embryos. Aurora kinases are evolutionarily conserved serine/threonine kinases and key regulators of mitosis. Aurora kinase B (AurkB) is ubiquitously expressed while Aurora kinase C (AurkC) is specifically expressed in gametes and preimplantation embryos. We found that increasing AurkC level in one blastomere of the 2-cell embryo accelerated cell division and decreasing AurkC level slowed down mitosis. Changing AurkB level had the opposite effect...
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28434118/hyperoside-inhibits-the-effects-induced-by-oxidized-low-density-lipoprotein-in-vascular-smooth-muscle-cells-via-oxldl-lox-1-erk-pathway
#2
Zhengyu Zhang, Dongdong Zhang, Baoling Du, Zhiqiang Chen
Hyperoside is a major active constituent in many medicinal plants traditionally used in Chinese medicines for their anti-inflammatory, antioxidative, and vascular protective effects. Recent studies have focused on the protective effects of hyperoside on hyperlipidemia. However, the molecular mechanisms underlying these effects are unknown. In this study, vascular smooth muscle cells (VSMCs) were treated in vitro with oxidized low-density lipoprotein (oxLDL) in the presence or absence of hyperoside. Western blotting, quantitative PCR, and tetrazolium assay were used to detect lectin-like oxLDL receptor-1 (LOX-1) expression and extracellular signal-regulated kinases (ERK) activation, and to determine VSMCs viability...
April 22, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28434110/the-risk-of-radiation-necrosis-following-stereotactic-radiosurgery-with-concurrent-systemic-therapies
#3
Joseph M Kim, Jacob A Miller, Rupesh Kotecha, Roy Xiao, Aditya Juloori, Matthew C Ward, Manmeet S Ahluwalia, Alireza M Mohammadi, David M Peereboom, Erin S Murphy, John H Suh, Gene H Barnett, Michael A Vogelbaum, Lilyana Angelov, Glen H Stevens, Samuel T Chao
To investigate late toxicity among patients with newly-diagnosed brain metastases undergoing stereotactic radiosurgery (SRS) with concurrent systemic therapies with or without whole-brain radiation therapy (WBRT). Patients with newly-diagnosed brain metastasis who underwent SRS at a single tertiary-care institution from 1997 to 2015 were eligible for inclusion. The class and timing of all systemic therapies were collected for each patient. The primary outcome was the cumulative incidence of radiographic radiation necrosis (RN)...
April 22, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28433997/argon-delays-initiation-of-liver-regeneration-after-partial-hepatectomy-in-rats
#4
Tom Florian Ulmer, Athanassious Fragoulis, Henriette Dohmeier, Andreas Kroh, Anne Andert, Christian Stoppe, Hamid Alizai, Christian Klink, Mark Coburn, Ulf Peter Neumann
BACKGROUND: The liver can heal up to restitutio ad integrum following damage resulting from various causes. Different studies have demonstrated the protective effect of argon on various cells and organs. To the best of our knowledge, the organ-protective effects of the noble gas argon on the liver have not yet been investigated, although argon appears to influence signal paths that are well-known mediators of liver regeneration. We hypothesized that argon inhalation prior to partial hepatectomy (70%) has a positive effect on the initiation of liver regeneration in rats...
April 22, 2017: European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes
https://www.readbyqxmd.com/read/28433992/the-aachen-minipig-phenotype-genotype-hematological-and-biochemical-characterization-and-comparison-to-the-g%C3%A3-ttingen-minipig
#5
Kerstin Pawlowsky, Lisa Ernst, Julia Steitz, Thaddäus Stopinski, Babette Kögel, Anna Henger, Reinhart Kluge, René Tolba
BACKGROUND: The pig is one of the most frequently used large animal models for biomedical research, especially in the field of translational research and surgical models. While standard livestock breeds are used in short-term and acute studies, minipig breeds are the preferred breeds in long-term and chronic studies due to their limited growth and body weight. OBJECTIVE: In consideration of the 3R principle (refinement, reduction, replacement) and the increasing demand, the aim of this study was to generate a new, robust, non-specific-pathogen-free minipig breed, the Aachen minipig...
April 22, 2017: European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes
https://www.readbyqxmd.com/read/28433945/cqmuh-011-a-novel-adamantane-sulfonamide-compound-inhibits-lipopolysaccharide-and-d-galactosamine-induced-fulminant-hepatic-failure-in-mice
#6
Liping Yan, Xiangnan Hu, Qihong Wu, Rong Jiang, Sisi Zhang, Qiao Ling, Hailin Liu, Xuejun Jiang, Jingyuan Wan, Yingju Liu
CQMUH-011, a novel adamantane sulfonamide compound, was shown to suppress macrophage activation and proliferation in our previous study. However, it is unknown whether CQMUH-011 has anti-inflammatory and hepatoprotective properties. In this study, we investigated the potential effects and mechanisms of CQMUH-011 on lipopolysaccharide (LPS)-induced RAW264.7 cell activation in vitro and LPS- and D-galactosamine (D-GalN)-induced fulminant hepatic failure (FHF) in vivo. The results showed that in RAW264.7 cells challenged by LPS, CQMUH-011 inhibited cell proliferation and induced cell cycle arrest and apoptosis...
April 20, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28433920/proteomic-analysis-of-sockeye-salmon-serum-as-a-tool-for-biomarker-discovery-and-new-insight-into-the-sublethal-toxicity-of-diluted-bitumen
#7
Sarah L Alderman, Laura A Dindia, Christopher J Kennedy, Anthony P Farrell, Todd E Gillis
Pipelines carrying diluted bitumen (dilbit) from Canada's oil sands traverse North America, including the freshwater habitat of Pacific salmon, posing a risk of environmental release and aquatic exposure. Swimming performance is impacted in juvenile sockeye (Oncorhynchus nerka) exposed to dilbit; therefore biomarkers of dilbit exposure will be valuable for monitoring at-risk salmon stocks. This study characterized changes in the serum proteome of sockeye exposed to a sub-lethal and environmentally relevant concentration of dilbit using isobaric tags for relative and absolute quantitation (iTRAQ), and included a range of experimental conditions to permit identification of biomarkers that are robust across time (1 and 4wk) and exercise level (at rest and following a swim test)...
April 12, 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/28433890/il-37-induces-autophagy-in-hepatocellular-carcinoma-cells-by-inhibiting-the-pi3k-akt-mtor-pathway
#8
Ting-Ting Li, Di Zhu, Tong Mou, Zhen Guo, Jun-Liang Pu, Qing-Song Chen, Xu-Fu Wei, Zhong-Jun Wu
Autophagy is an intracellular "self-eating" process that is closely related to inflammation and cellular immunity. New studies indicate that autophagy is also involved in tumor suppression. The anti-inflammatory cytokine interleukin-37 (IL-37) has been shown to have tumor-suppressive abilities in hepatocellular carcinoma (HCC). Notably, autophagy appears to play a dual role in the development of HCC and may be involved in both tumorigenesis and tumor suppression. However, the potential role of IL-37 in autophagy is currently unknown...
April 20, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28433747/chemical-composition-of-ocimum-sanctum-by-lc-esi-ms-ms-analysis-and-its-protective-effects-against-smoke-induced-lung-and-neuronal-tissue-damage-in-rats
#9
M P Venuprasad, Hemanth Kumar Kandikattu, Sakina Razack, Narayanappa Amruta, Farhath Khanum
Smoke induced oxidative stress is known to cause various cancers and associated health problems including lung cancer. Herbal extracts have been reported as antioxidant supplements which attenuate free radical induced oxidative damage of tissues, among which Ocimum sanctum has been reported as the elixir of life due to its innumerable health benefits. In the present study, we investigated the protective effect of O. sanctum against cracker smoke induced lung and brain tissue damage. The results of the study demonstrate that O...
April 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28433679/part-i-design-synthesis-and-biological-evaluation-of-novel-pyrazole-benzimidazole-conjugates-as-checkpoint-kinase-2-chk2-inhibitors-with-studying-their-activities-alone-and-in-combination-with-genotoxic-drugs
#10
Shadia A Galal, Ahmed S Abdelsamie, Samia A Shouman, Yasmin M Attia, Hamed I Ali, Ashraf Tabll, Reem El-Shenawy, Yasmine S El Abd, Mamdouh M Ali, Abeer E Mahmoud, Abeer H Abdel-Halim, Amal A Fyiad, Adel S Girgis, Hoda I El-Diwani
Activated checkpoint kinase 2 (Chk2) is a tumor suppressor as one of the main enzymes that affect the cell cycle. 2-Biarylbenzimidazoles are potent selective class of Chk2 inhibitors; the structure-based design was applied to synthesize a new series of this class with replacing the lateral aryl group by substituted pyrazoles. Ten pyrazole-benzimidazole conjugates from the best fifty candidates according to docking programs have been subjected to chemical synthesis in this study. The activities of the conjugates 5-14 as checkpoint kinase inhibitors and as antitumor alone and in combination with genotoxic drugs were evaluated...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28433634/dual-sphingosine-kinase-inhibitor-ski-ii-enhances-sensitivity-to-5-fluorouracil-in-hepatocellular-carcinoma-cells-via-suppression-of-osteopontin-and-fak-igf-1r-signalling
#11
Petra Grbčić, Ivana Tomljanović, Marko Klobučar, Sandra Kraljević Pavelić, Ksenija Lučin, Mirela Sedić
Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related deaths globally. Although 5-Fluorouracil (5-FU) is used as the first choice treatment for advanced HCC, it exerts poor efficacy and is associated with acquired and intrinsic resistance. Sphingosine kinases (Sphk) 1 and 2 play tumour-promoting roles in different cancer types including HCC and thus represent promising pharmacological targets. In the present study, we have investigated for the first time the anticancer efficacy and underlying molecular mechanisms of combined administration of 5-FU and dual Sphk1/Sphk2 inhibitor SKI-II (4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol) in HepG2 hepatocellular carcinoma cells...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28433631/detection-of-camp-and-of-pka-activity-in-saccharomyces-cerevisiae-single-cells-using-fluorescence-resonance-energy-transfer-fret-probes
#12
Sonia Colombo, Serena Broggi, Maddalena Collini, Laura D'Alfonso, Giuseppe Chirico, Enzo Martegani
In Saccharomyces cerevisiae the second messenger cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) play a central role in metabolism regulation, stress resistance and cell cycle progression. To monitor cAMP levels and PKA activity in vivo in single S. cerevisiae cells, we expressed an Epac-based FRET probe and a FRET-based A-kinase activity reporter, which were proven to be useful live-cell biosensors for cAMP levels and PKA activity in mammalian cells. Regarding detection of cAMP in single yeast cells, we show that in wild type strains the CFP/YFP fluorescence ratio increased immediately after glucose addition to derepressed cells, while no changes were observed when glucose was added to a strain that is not able to produce cAMP...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28433628/ca-2-dependent-hyperpolarization-hypothesis-for-mammalian-sleep
#13
REVIEW
Fumiya Tatsuki, Koji L Ode, Hiroki R Ueda
The detailed molecular mechanisms underlying the regulation of sleep/wake cycles in mammals are elusive. In this regulation, at least two mechanisms with fast and slow time scales are involved. In the faster time scale, a state of non-rapid-eye-movement (NREM) sleep can be microscopically characterized by the millisecond-to-second-order electrical behavior of neurons, namely slow-wave oscillations described by electrophysiology. In the slower time scale, the total duration of NREM sleep is homeostatically regulated by sleep pressure (the need for sleep), which is usually sustained for hours or even days and can be macroscopically described by electroencephalogram (EEG)...
April 19, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28433539/rationally-designed-pi3k%C3%AE-mutants-to-mimic-atr-and-their-use-to-understand-binding-specificity-of-atr-inhibitors
#14
Yipin Lu, Mark Knapp, Kenneth Crawford, Robert Warne, Robert Elling, Kelly Yan, Michael Doyle, Gwynn Pardee, Li Zhang, Sylvia Ma, Mulugeta Mamo, Elizabeth Ornelas, Yue Pan, Dirksen Bussiere, Johanna Jansen, Isabel Zaror, Albert Lai, Paul Barsanti, Janet Sim
ATR, a protein kinase in the PIKK family, plays a critical role in the cell DNA-damage response and is an attractive anticancer drug target. Several potent and selective inhibitors of ATR have been reported showing significant antitumor efficacy, with most advanced ones entering clinical trials. However, due to the absence of an experimental ATR structure, the determinants contributing to ATR inhibitors' potency and specificity are not well understood. Here we present the mutations in the ATP-binding site of PI3Kα to progressively transform the pocket to mimic that of ATR...
April 19, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28433077/development-and-clinical-utility-of-a-blood-based-test-service-for-the-rapid-identification-of-actionable-mutations-in-non-small-cell-lung-carcinoma
#15
Hestia Mellert, Trudi Foreman, Leisa Jackson, Dianna Maar, Scott Thurston, Kristina Koch, Amanda Weaver, Samantha Cooper, Nicholas Dupuis, Ubaradka G Sathyanarayana, Jakkie Greer, Westen Hahn, Dawne Shelton, Paula Stonemetz, Gary A Pestano
Nearly 80% of cancer patients do not have genetic mutation results available at initial oncology consultation; up to 25% of patients begin treatment before receiving their results. These factors hinder the ability to pursue optimal treatment strategies. This study validates a blood-based genome-testing service that provides accurate results within 72 hours. We focused on targetable variants in advanced non-small cell lung carcinoma-epidermal growth factor receptor gene (EGFR) variant L858R, exon 19 deletion (ΔE746-A750), and T790M; GTPase Kirsten ras gene (KRAS) variants G12C/D/V; and echinoderm microtubule associated protein like and 4 anaplastic lymphoma receptor tyrosine kinase fusion (EML4-ALK) transcripts 1/2/3...
May 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28433076/identification-of-ntrk3-fusions-in-childhood-melanocytic-neoplasms
#16
Lu Wang, Klaus J Busam, Ryma Benayed, Robert Cimera, Jiajing Wang, Ryan Denley, Mamta Rao, Ruth Aryeequaye, Kerry Mullaney, Long Cao, Marc Ladanyi, Meera Hameed
Spitzoid neoplasms are a distinct group of melanocytic tumors. Genetically, they lack mutations in common melanoma-associated oncogenes. Recent studies have shown that spitzoid tumors may contain a variety of kinase fusions, including ROS1, NTRK1, ALK, BRAF, and RET fusions. We report herein the discovery of recurrent NTRK3 gene rearrangements in childhood melanocytic neoplasms with spitzoid and/or atypical features, based on genome-wide copy number analysis by single-nucleotide polymorphism array, which showed intragenic copy number changes in NTRK3...
May 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28433068/the-role-of-interleukin-1%C3%AE-and-extracellular-signal-regulated-kinase-1-2-in-glucose-stimulated-insulin-secretion
#17
Ben Niu, Heng Su, Xue-Shan Xia, Qiu He, Yuan-Ming Xue, Xin-Ming Yan
Glucose-stimulated insulin secretion (GSIS) is one of the important physiological characteristics of islet β cells, and extracellular-regulated protein kinase 1/2 (ERK1/2) is an important member of the mitogen-activated protein kinase family that regulates this process. The inflammatory cytokine interleukin (IL)-1β can inhibit the insulin secretion of pancreatic β cells, but the exact mechanism is unclear. This study was designed to investigate the inhibitory effect of IL-1β on GSIS in βTC-6 cells and its relation with the ERK1/2 signal transduction pathway...
May 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28432946/design-and-synthesis-of-sulfonamide-substituted-diphenylpyrimidines-sfa-dppys-as-potent-bruton-s-tyrosine-kinase-btk-inhibitors-with-improved-activity-toward-b-cell-lymphoblastic-leukemia
#18
He Liu, Menghua Qu, Lina Xu, Xu Han, Changyuan Wang, Xiaohong Shu, Jihong Yao, Kexin Liu, Jinyong Peng, Yanxia Li, Xiaodong Ma
A new series of diphenylpyrimidine derivatives (SFA-DPPYs) were synthesized by introducing a functional sulfonamide into the C-2 aniline moiety of pyrimidine template, and then were biologically evaluated as potent Bruton's tyrosine kinase (BTK) inhibitors. Among these molecules, inhibitors 10c, 10i, 10j and 10k displayed high potency against the BTK enzyme, with IC50 values of 1.18 nM, 0.92 nM, 0.42 nM and 1.05 nM, respectively. In particular, compound 10c could remarkably inhibit the proliferation of the B lymphoma cell lines at concentrations of 6...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28432877/maternal-low-protein-diet-decreases-brain-derived-neurotrophic-factor-expression-in-the-brains-of-the-neonatal-rat-offspring
#19
Gurdeep Marwarha, Kate Claycombe-Larson, Jared Schommer, Othman Ghribi
Prenatal exposure to a maternal low-protein (LP) diet has been known to cause cognitive impairment, learning and memory deficits. However, the underlying mechanisms have not been identified. Herein, we demonstrate that a maternal LP diet causes, in the brains of the neonatal rat offspring, an attenuation in the basal expression of the brain-derived neurotrophic factor (BDNF), a neurotrophin indispensable for learning and memory. Female rats were fed either a 20% normal protein (NP) diet or an 8% LP 3 weeks before breeding and during the gestation period...
April 6, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28432840/detection-of-egfr-mutations-in-patients-with-non-small-cell-lung-cancer-by-high-resolution-melting-comparison-with-other-methods
#20
Carlos Martínez-Carretero, Fernando Iguaz Pascual, Antonio Rus, Ivan Bernardo
BACKGROUND: The discovery of mutations in the epidermal growth factor receptor gene (EGFR) related to the clinical response to tyrosine kinase inhibitors, has transformed the management of non-small cell lung cancer (NSCLC). Several methods have been developed for determination of mutations in EGFR, with different sensitivity and potential ability to detect a different number of mutations. METHODS: We developed a screening method by high resolution melting (HRM) to detect EGFR mutations, and compared the results of 123 fixed in formalin and paraffin embedded (FFPE) tumor tissue samples with the detection of mutations by allele-specific PCR...
April 22, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
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