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https://www.readbyqxmd.com/read/28343379/hepatitis-c-virus-nonstructural-5a-protein-hcv-ns5a-inhibits-hepatocyte-apoptosis-through-the-nf-kappab-mir-503-bcl-2-pathway
#1
Xie Zheng Yuan, Xiao Zhi Hua, Wang Fen Fen
The nonstructural protein 5A (NS5A) encoded by the human hepatitis C virus (HCV) RNA genome is a multifunctional phosphoprotein. To analyse the influence of NS5A on apoptosis, we established an Hep-NS5A cell line (HepG2 cells that stably express NS5A) and induced apoptosis using tumour necrosis factor (TNF)-alpha. We utilised the MTT assay to detect cell viability, real-time quantitative polymerase chain reaction and Western blot to analyse gene and protein expression, and a luciferase reporter gene experiment to investigate the targeted regulatory relationship...
March 27, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28343377/protein-kinase-c-mediates-the-corticosterone-induced-sensitization-of-dorsal-root-ganglion-neurons-innervating-the-rat-stomach
#2
Meng Li, Lu Xue, Hong-Yan Zhu, Hongjun Wang, Xue Xu, Geping Wu, Guang-Yin Xu
Background/Aims: Gastric hypersensitivity contributes to abdominal pain in patients with functional dyspepsia (FD). Recent studies showed that hormones induced by stress are correlated with visceral hypersensitivity. However, the precise mechanisms underlying gastric hypersensitivity remain largely unknown. The aim of the present study was designed to investigate the roles of corticosterone (CORT) on excitability of dorsal root ganglion (DRG) neurons innervating the stomach. Methods: DRG neurons innervating the stomach were labeled by DiI injection into the stomach wall...
March 26, 2017: Journal of Neurogastroenterology and Motility
https://www.readbyqxmd.com/read/28343375/foxo1-suppression-is-a-determinant-of-acquired-lapatinib-resistance-in-her2-positive-gastric-cancer-cells-through-met-upregulation
#3
Jinju Park, Yiseul Choi, Young San Ko, Younghoon Kim, Jung-Soo Pyo, Bo Gun Jang, Min A Kim, Jae-Seon Lee, Mee Soo Chang, Jong-Wan Park, Byung Lan Lee
Purpose: Lapatinib is a candidate drug for treatment of trastuzumab-resistant, HER2-positive gastric cancer (GC). Unfortunately, lapatinib resistance renders this drug ineffective. The present study investigated the implication of forkhead box protein O1 (FOXO1) signaling in the acquired lapatinib resistance in HER2-positive GC cells. Materials and Methods: Lapatinib-resistant GC cell lines (SNU-216 LR2-8) were generated in vitro by chronic exposure of lapatinib-sensitive, HER2-positive SNU-216 cells to lapatinib...
March 24, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28343347/bioanalysis-of-farnesyl-pyrophosphate-in-human-plasma-by-high-performance-liquid-chromatography-coupled-to-triple-quadrupole-tandem-mass-spectrometry-and-hybrid-quadrupole-orbitrap-high-resolution-mass-spectrometry
#4
Hiroshi Sugimoto, Mie Iguchi, Fumihiro Jinno
The isoprenoids farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) are pivotal intermediates for cholesterol homeostasis and cell signaling in the mevalonate pathway. We developed a sensitive and selective high-performance liquid chromatography tandem triple quadrupole mass spectrometry (LC-QQQ-MS) method for FPP in human plasma without the need for a derivatization process. We optimized the sample preparation procedure to extract FPP and (13)C5-FPP (as internal standard) from sample fluids using methanol...
March 25, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28343311/mechanistic-insight-of-platelet-apoptosis-leading-to-non-surgical-bleeding-among-heart-failure-patients-supported-by-continuous-flow-left-ventricular-assist-devices
#5
Nandan K Mondal, Tielou Li, Zengsheng Chen, Hegang H Chen, Erik N Sorensen, Si M Pham, Michael A Sobieski, Steven C Koenig, Mark S Slaughter, Bartley P Griffith, Zhongjun J Wu
Non-surgical bleeding (NSB) is the most common clinical complication in heart failure (HF) patients supported by continuous-flow left ventricular assist devices (CF-LVADs). In this study, oxidative stress and alteration of signal pathways leading to platelet apoptosis were investigated. Thirty-one HF patients supported by CF-LVADs were divided into bleeder (n = 12) and non-bleeder (n = 19) groups. Multiple blood samples were collected at pre-implant (baseline) and weekly up to 1-month post-implant. A single blood sample was collected from healthy subjects (reference)...
March 25, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28343310/steroidogenic-genes-expressions-are-repressed-by-high-levels-of-leptin-and-the-jak-stat-signaling-pathway-in-ma-10-leydig-cells
#6
David A Landry, François Sormany, Josée Haché, Pauline Roumaud, Luc J Martin
The adipose tissue is an important endocrine organ secreting numerous peptide hormones, including leptin. Increased circulating levels of leptin, as a result of hormonal resistance in obese individuals, may contribute to lower androgen production in obese males. However, the molecular mechanisms involved need to be better defined. Androgens are mainly produced by Leydig cells within the testis. In male rodents, activation of the leptin receptor modulates a cascade of intracellular signal transduction pathways which may lead to regulation of transcription factors having influences on steroidogenesis in Leydig cells...
March 25, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28343297/association-of-the-cx3cr1-v249i-variant-with-neurofibrillary-pathology-progression-in-late-onset-alzheimer-s-disease
#7
Alan López-López, Ellen Gelpi, Diana Maria Lopategui, Jose M Vidal-Taboada
Neuroinflammation and microglial dysfunction have a prominent role in the pathogenesis of late-onset Alzheimer's disease (LOAD). CX3CR1 is a microglia-specific gene involved in microglia-neuron crosstalk and neuroinflammation. Numerous evidence show the involvement of CX3CR1 in AD. The aim of this study was to investigate if some functional genetic variants of this gene could influence on LOAD's outcome, in a neuropathologically confirmed Spanish cohort. We designed an open, pragmatic, case-control retrospective study including a total of 475 subjects (205 pathologically confirmed AD cases and 270 controls)...
March 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28343294/neuroprotective-role-of-exogenous-brain-derived-neurotrophic-factor-in-hypoxia-hypoglycemia-induced-hippocampal-neuron-injury-via-regulating-trkb-mir134-signaling
#8
Weidong Huang, Facai Meng, Jie Cao, Xiaobin Liu, Jie Zhang, Min Li
Hypoxic-ischemic brain injury is an important cause of neonatal mortality and morbidity. Brain-derived neurotrophic factor (BDNF) has been reported to play a neuroprotective role in hypoxic-ischemic brain injury; however, the specific effects and mechanism of BDNF on hypoxic-hypoglycemic hippocampal neuron injury remains unknown. The current study investigated the action of BDNF in regulating cerebral hypoxic-ischemic injury by simulating hippocampal neuron ischemia and hypoxia. We found that BDNF, p-Trkb, and miR-134 expression levels decreased, and that exogenous BDNF increased survival and reduced apoptosis in hypoxic-hypoglycemic hippocampal neurons...
March 26, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28343293/pharmacokinetic-and-pharmacodynamic-considerations-in-the-treatment-of-chronic-lymphocytic-leukemia-ibrutinib-idelalisib-and-venetoclax
#9
REVIEW
Madeline Waldron, Allison Winter, Brian T Hill
Management of chronic lymphocytic leukemia has changed markedly over the last several years with the emergence of several novel oral agents targeting B-cell receptor and Bcl-2 signaling pathways. For patients requiring treatment, ibrutinib, idelalisib, and venetoclax offer unique clinical benefits with a different set of therapeutic considerations compared with traditional parenteral therapy. Despite the conveniences afforded by oral therapy, these agents also carry unique logistical obstacles. Drug interactions with agents that are metabolized via the cytochrome P450 3A4 pathway are possible with all three agents...
March 25, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28343277/pancreatic-alpha-cell-selective-deletion-of-tcf7l2-impairs-glucagon-secretion-and-counter-regulatory-responses-to-hypoglycaemia-in-mice
#10
Gabriela da Silva Xavier, Angeles Mondragon, Vishnou Mourougavelou, Céline Cruciani-Guglielmacci, Jessica Denom, Pedro Luis Herrera, Christophe Magnan, Guy A Rutter
AIMS/HYPOTHESIS: Transcription factor 7-like 2 (TCF7L2) is a high mobility group (HMG) box-containing transcription factor and downstream effector of the Wnt signalling pathway. SNPs in the TCF7L2 gene have previously been associated with an increased risk of type 2 diabetes in genome-wide association studies. In animal studies, loss of Tcf7l2 function is associated with defective islet beta cell function and survival. Here, we explore the role of TCF7L2 in the control of the counter-regulatory response to hypoglycaemia by generating mice with selective deletion of the Tcf7l2 gene in pancreatic alpha cells...
March 25, 2017: Diabetologia
https://www.readbyqxmd.com/read/28343235/transcription-dependent-radial-distribution-of-tcf7l2-regulated-genes-in-chromosome-territories
#11
Keyvan Torabi, Darawalee Wangsa, Immaculada Ponsa, Markus Brown, Anna Bosch, Maria Vila-Casadesús, Tatiana S Karpova, Maria Calvo, Antoni Castells, Rosa Miró, Thomas Ried, Jordi Camps
Human chromosomes occupy distinct territories in the interphase nucleus. Such chromosome territories (CTs) are positioned according to gene density. Gene-rich CTs are generally located in the center of the nucleus, while gene-poor CTs are positioned more towards the nuclear periphery. However, the association between gene expression levels and the radial positioning of genes within the CT is still under debate. In the present study, we performed three-dimensional fluorescence in situ hybridization experiments in the colorectal cancer cell lines DLD-1 and LoVo using whole chromosome painting probes for chromosomes 8 and 11 and BAC clones targeting four genes with different expression levels assessed by gene expression arrays and RT-PCR...
March 25, 2017: Chromosoma
https://www.readbyqxmd.com/read/28343223/sildenafil-enhances-quantity-of-immature-neurons-and-promotes-functional-recovery-in-the-developing-ischemic-mouse-brain
#12
Jonas Engels, Natalie Elting, Lisa Braun, Ivo Bendix, Josephine Herz, Ursula Felderhoff-Müser, Mark Dzietko
BACKGROUND: Hypoxic-ischemic (HI) injury to the developing brain occurs in 1 out of 1,000 live births and remains a major cause of significant morbidity and mortality. A large number of survivors suffer from long-term sequelae including seizures and neurological deficits. However, the pathophysiological mechanisms of recovery after HI insult are not clearly understood, and preventive measures or clinical treatments are nonexistent or not sufficiently effective in the clinical setting...
March 25, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28343214/moderate-grade-germinal-matrix-haemorrhage-activates-cell-division-in-the-neonatal-mouse-subventricular-zone
#13
William J Dawes, Xinyu Zhang, Stephen P J Fancy, David Rowitch, Silvia Marino
Precise temporal and spatial control of the neural stem/progenitor cells within the subventricular zone (SVZ) germinal matrix of the brain is important for normal development in the third trimester and the early postnatal period. The high metabolic demands of proliferating germinal matrix precursors, coupled with the flimsy structure of the germinal matrix cerebral vasculature, are thought to account for the high rates of haemorrhage in extremely- and very-low-birth-weight preterm infants. Germinal matrix haemorrhage can commonly extend to intraventricular haemorrhage (IVH)...
March 25, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28343163/s100a6-focus-on-recent-developments
#14
Wiesława Leśniak, Tomasz Wilanowski, Anna Filipek
The Ca2+-binding protein, S100A6, belongs to the S100 family. Binding of Ca2+ induces a conformational change, which causes an increase in the overall S100A6 hydrophobicity and allows it to interact with many targets. S100A6 is expressed in different normal tissues and in many tumors. Up to now it has been shown that S100A6 is involved in cell proliferation, cytoskeletal dynamics and tumorigenesis, and that it might have some extracellular functions. In this review, we summarize novel discoveries concerning S100A6 targets, its involvement in cellular signaling pathways, and presence in stem/progenitor cells, extracellular matrix and body fluids of diseased patients...
March 25, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28343148/de-novo-mutations-in-cbl-causing-early-onset-paediatric-moyamoya-angiopathy
#15
Stéphanie Guey, Lou Grangeon, Francis Brunelle, Françoise Bergametti, Jeanne Amiel, Stanislas Lyonnet, Audrey Delaforge, Minh Arnould, Béatrice Desnous, Céline Bellesme, Dominique Hervé, Jan C Schwitalla, Markus Kraemer, Elisabeth Tournier-Lasserve, Manoelle Kossorotoff
BACKGROUND: Moyamoya angiopathy (MMA) is characterised by a progressive stenosis of the terminal part of the internal carotid arteries and the development of abnormal collateral deep vessels. Its pathophysiology is unknown. MMA can be the sole manifestation of the disease (moyamoya disease) or be associated with various conditions (moyamoya syndrome) including some Mendelian diseases. We aimed to investigate the genetic basis of moyamoya using a whole exome sequencing (WES) approach conducted in sporadic cases without any overt symptom suggestive of a known Mendelian moyamoya syndrome...
March 25, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28343145/effects-of-tiletamine-on-the-adenosine-monophosphate-activated-protein-kinase-signaling-pathway-in-the-rat-central-nervous-system
#16
Li-Xue Su, Xing-Xing Shi, Peng Yang, Hao Chen, Xin Li, Hong-Gang Fan, Hong-Bin Wang
OBJECTIVE: The dissociative anesthetic tiletamine, which acts on the central nervous system (CNS), is widely used in veterinary medicine and animal experiments. Recent studies indicate that adenosine 5'-monophosphate activated protein kinase (AMPK) plays a key role in the analgesic action of tiletamine. In the present study, the effects of tiletamine on the AMPK signaling pathway in rats were investigated. METHODS: Sprague-Dawley rats were injected intraperitoneally with tiletamine and executed at 10, 20, 40 and 60min post injection...
March 21, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28343144/gene-and-protein-expressions-and-metabolomics-exhibit-activated-redox-signaling-and-wnt-%C3%AE-catenin-pathway-are-associated-with-metabolite-dysfunction-in-patients-with-chronic-kidney-disease
#17
Dan-Qian Chen, Gang Cao, Hua Chen, Dan Liu, Wei Su, Xiao-Yong Yu, Nosratola D Vaziri, Xiu-Hua Liu, Xu Bai, Li Zhang, Ying-Yong Zhao
Changes in plasma concentration of small organic metabolites could be due to their altered production or urinary excretion and changes in their urine concentration may be due to the changes in their filtered load, tubular reabsorption, and/or altered urine volume. Therefore, these factors should be considered in interpretation of the changes observed in plasma or urine of the target metabolite(s). Fasting plasma and urine samples from 180 CKD patients and 120 age-matched healthy controls were determined by UPLC-HDMS-metabolomics and quantitative real-time RT-PCR techniques...
March 23, 2017: Redox Biology
https://www.readbyqxmd.com/read/28343126/pi3k-signaling-in-cancer-beyond-akt
#18
REVIEW
Evan C Lien, Christian C Dibble, Alex Toker
The phosphoinositide 3-kinase (PI3K) signaling pathway is one of the most frequently altered pathways in human cancer and has a critical role in driving tumor initiation and progression. Although PI3K and its lipid product phosphatidylinositol-3,4,5-trisphosphate (PIP3) have been shown to activate multiple downstream signaling proteins, the vast majority of studies have focused on the protein kinase AKT as the dominant effector of PI3K signaling. However, recent studies have demonstrated many contexts under which other PIP3-dependent signaling proteins critically contribute to cancer progression, illustrating the importance of understanding AKT-independent signaling downstream of PI3K...
March 23, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28343122/genetic-and-epigenetic-variation-of-transposable-elements-in-arabidopsis
#19
REVIEW
Charles J Underwood, Ian R Henderson, Robert A Martienssen
Transposable elements are mobile genetic elements that are prevalent in plant genomes and are silenced by epigenetic modification. Different epigenetic modification pathways play distinct roles in the control of transposable element transcription, replication and recombination. The Arabidopsis genome contains families of all of the major transposable element classes, which are differentially enriched in particular genomic regions. Whole genome sequencing and DNA methylation profiling of hundreds of natural Arabidopsis accessions has revealed that transposable elements exhibit significant intraspecific genetic and epigenetic variation, and that genetic variation often underlies epigenetic variation...
March 23, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28343095/ion-mobility-mass-spectrometry-and-orthogonal-gas-phase-techniques-to-study-amyloid-formation-and-inhibition
#20
REVIEW
Waldemar Hoffmann, Gert von Helden, Kevin Pagel
Amyloidogenic peptide oligomers are responsible for a variety of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Due to their dynamic, polydisperse, and polymorphic nature, these oligomers are very challenging to characterize using traditional condensed-phase methods. In the last decade, ion mobility-mass spectrometry (IM-MS) and related gas-phase techniques have emerged as a powerful alternative to disentangle the structure and assembly characteristics of amyloid forming systems. This review highlights recent advances in which IM-MS was used to characterize amyloid oligomers and their underlying assembly pathway...
March 23, 2017: Current Opinion in Structural Biology
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