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https://www.readbyqxmd.com/read/29232766/combined-erlotinib-and-pf-03084014-treatment-contributes-to-synthetic-lethality-in-head-and-neck-squamous-cell-carcinoma
#1
Yang Zheng, Zhao Wang, Xu Ding, Yibo Dong, Wei Zhang, Wei Zhang, Yi Zhong, Wenyi Gu, Yunong Wu, Xiaomeng Song
OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) is characterized by high mortality and low survival rates. As an epidermal growth factor receptor (EGFR) inhibitor, Erlotinib has been approved for treatment of various tumours. PF-03084014 is a selective inhibitor of Notch1 signalling. This study aimed to explore new approaches for simultaneously targeting EGFR and Notch1 signalling to attenuate tumour growth and improve survival. MATERIALS AND METHODS: Cell proliferation was determined by CCK-8 assay and Flow cytometry...
December 12, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/29232732/high-salt-intake-promotes-different-responses-to-urodilatin-and-uroguanylin-in-the-isolated-rat-kidney
#2
Antonio Rafael Coelho Jorge, Pedro Henrique Sá Costa, Helena Serra Azul Monteiro, Manassés Claudino Fonteles
Urodilatin (UD) and uroguanylin (UGN) have been implicated in the regulation of salt and water homeostasis, particularly in the balance handling of salt intake. In this sense, the aim of the present work was to study the main effects of these peptides in kidneys from animals subjected to high NaCl (2%) intake, during 10 days in metabolic cages. The control group received only normal water, whereas the treated group drank 2% solution of NaCl (NaCl 2%). In addition, we studied effect of subthreshold UD (0.14 nM) and UGN (0...
December 12, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29232711/dependence-of-prevalence-of-contiguous-pathways-in-proteins-on-structural-complexity
#3
Kelly M Thayer, Jesse C Galganov, Avram J Stein
Allostery is a regulatory mechanism in proteins where an effector molecule binds distal from an active site to modulate its activity. Allosteric signaling may occur via a continuous path of residues linking the active and allosteric sites, which has been suggested by large conformational changes evident in crystal structures. An alternate possibility is that the signal occurs in the realm of ensemble dynamics via an energy landscape change. While the latter was first proposed on theoretical grounds, increasing evidence suggests that such a control mechanism is plausible...
2017: PloS One
https://www.readbyqxmd.com/read/29232706/biventricular-differences-in-%C3%AE-adrenergic-receptor-signaling-following-burn-injury
#4
Ashley N Guillory, Robert P Clayton, Anesh Prasai, Amina El Ayadi, David N Herndon, Celeste C Finnerty
Burn injury detrimentally affects the myocardium, primarily due to over-activation of β-adrenergic receptors (β-AR). Autopsy reports from our institution reveal that patients often suffer from right ventricle (RV) failure. Since burn injury affects β-AR signaling in the left ventricle (LV), we proposed that β-AR signaling may also be altered in the RV. A rodent model with a scald burn of 60% of the total body surface area was used to test this hypothesis. Ventricles were isolated 7 days post-burn. We examined the expression of β-ARs via Western blotting and the mRNA expression of downstream signaling proteins via qRT-PCR...
2017: PloS One
https://www.readbyqxmd.com/read/29232699/cxcr4-blockade-decreases-cd4-t-cell-exhaustion-and-improves-survival-in-a-murine-model-of-polymicrobial-sepsis
#5
Kimberly M Ramonell, Wenxiao Zhang, Annette Hadley, Ching-Wen Chen, Katherine T Fay, John D Lyons, Nathan J Klingensmith, Kevin W McConnell, Craig M Coopersmith, Mandy L Ford
Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis...
2017: PloS One
https://www.readbyqxmd.com/read/29232696/effect-of-temperature-on-fatty-acid-metabolism-in-skeletal-muscle-mitochondria-of-untrained-and-endurance-trained-rats
#6
Jerzy A Zoladz, Agnieszka Koziel, Izabela Broniarek, Andrzej M Woyda-Ploszczyca, Karolina Ogrodna, Joanna Majerczak, Jan Celichowski, Zbigniew Szkutnik, Wieslawa Jarmuszkiewicz
We studied the effects of various assay temperatures, representing hypothermia (25°C), normothermia (35°C), and hyperthermia (42°C), on the oxidation of lipid-derived fuels in rat skeletal muscle mitochondria of untrained and endurance-trained rats. Adult 4-month-old male Wistar rats were assigned to a training group (rats trained on a treadmill for 8 weeks) or a sedentary control group. In skeletal muscle mitochondria of both control and trained rats, an increase in the assay temperature from 25°C to 42°C was accompanied by a consistent increase in the oxidation of palmitoylcarnitine and glycerol-3-phosphate...
2017: PloS One
https://www.readbyqxmd.com/read/29232694/hyperbranched-poly-%C3%AF%C2%B5-lysine-substrate-presenting-the-laminin-sequence-yigsr-induces-the-formation-of-spheroids-in-adult-bone-marrow-stem-cells
#7
Valeria Perugini, Steve T Meikle, Anna L Guildford, Matteo Santin
Unlike the fibroblast-like cells formed upon monolayer culture of human mesenchymal stem cells, the natural stem cell niche of the bone marrow and other types of tissues favours the formation of 3-dimensional (3D) cell clusters. The structuring and biological activity of these clusters are regulated by the contacts established by cells with both the basement membrane and neighbour cells and results in their asymmetric division and the consequent maintenance of both a stem population and a committed progeny...
2017: PloS One
https://www.readbyqxmd.com/read/29232693/host-factors-that-promote-retrotransposon-integration-are-similar-in-distantly-related-eukaryotes
#8
Sudhir Kumar Rai, Maya Sangesland, Michael Lee, Caroline Esnault, Yujin Cui, Atreyi Ghatak Chatterjee, Henry L Levin
Retroviruses and Long Terminal Repeat (LTR)-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs) encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration...
December 12, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29232653/salicylic-acid-and-broad-spectrum-of-nbs-lrr-family-genes-are-involved-in-smv-soybean-interactions
#9
Qiqi Zhao, Haina Li, Hongyu Sun, Aoga Li, Shuxin Liu, Ruonan Yu, Xiuqi Cui, Dejian Zhang, Hada Wuriyanghan
Soybean mosaic virus (SMV) is a severe pathogen reducing crop yield and seed quality of soybean. Although several resistance gene loci including Rsv1, Rsv3 and Rsv4 are identified in some soybean varieties, most of the soybean genes related to SMV infection are still not characterized. In order to reveal genome-wide gene expression profiles in response to SMV infection, we used transcriptome analysis to determine SMV-responsive genes in susceptible variety Hefeng25. Time course RNA-seq analysis at 1, 5 and 10 dpi identified many deregulated pathways and gene families...
December 7, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29232652/effect-of-ornithine-decarboxylase-and-norspermidine-in-modulating-cell-division-in-the-green-alga-chlamydomonas-reinhardtii
#10
Annalisa Tassoni, Nahid Awad, Gareth Griffiths
The extensive genetic resources of Chlamydomonas has led to its widespread use as a model system for understanding fundamental processes in plant cells, including rates of cell division potentially modulated through polyamines. Putrescine was the major polyamine in both free (88%) and membrane-bound fractions (93%) while norspermidine was the next most abundant in these fractions accounting for 11% and 6%, respectively. Low levels of diaminopropane, spermidine and spermine were also observed although no cadaverine or norspermine were detected...
December 7, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29232648/template-directed-fabrication-of-mil-101-cr-mesoporous-silica-composite-layer-packed-structure-and-enhanced-performance-for-co2-capture
#11
Chong Chen, Nengjie Feng, Qirui Guo, Zhong Li, Xue Li, Jing Ding, Lei Wang, Hui Wan, Guofeng Guan
A novel hybrid material constituted of MIL-101(Cr) and mesoporous silica was successfully assembled through an in-situ hydrothermal method. The MCM-41 with well-ordered mesopores acted as the structure-directing agent, which regulated the growth of MIL-101(Cr) crystals along a certain direction and restricted the expansion of framework. Meanwhile, the hydroxyl groups existed in MCM-41 preferentially coordinated with the Cr3+ centers in MOF, followed by the layer-packed arrangement of MIL-101(Cr) nanocrystals on the surface of matrix...
December 5, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/29232645/pre-optimization-of-spinal-surgery-patients-development-of-a-neurosurgical-enhanced-recovery-after-surgery-eras-protocol
#12
Zarina S Ali, Tracy S Ma, Ali K Ozturk, Neil R Malhotra, James M Schuster, Paul J Marcotte, M Sean Grady, William C Welch
OBJECTIVE: Despite surgical, technological, medical, and anesthetic improvements, patient outcomes following elective neurosurgical procedures can be associated with high morbidity. Enhanced recovery after surgery (ERAS) protocols are multimodal care pathways designed to optimize patient outcomes by addressing pre-, peri-, and post-operative factors. Despite significant data suggesting improved patient outcomes with the adoption of these pathways, development and implementation has been limited in the neurosurgical population...
December 8, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/29232622/cognitive-mechanisms-underlying-third-graders-arithmetic-skills-expanding-the-pathways-to-mathematics-model
#13
Ulf Träff, Linda Olsson, Kenny Skagerlund, Rickard Östergren
A modified pathways to mathematics model was used to examine the cognitive mechanisms underlying arithmetic skills in third graders. A total of 269 children were assessed on tasks tapping the four pathways and arithmetic skills. A path analysis showed that symbolic number processing was directly supported by the linguistic and approximate quantitative pathways. The direct contribution from the four pathways to arithmetic proficiency varied; the linguistic pathway supported single-digit arithmetic and word problem solving, whereas the approximate quantitative pathway supported only multi-digit calculation...
December 9, 2017: Journal of Experimental Child Psychology
https://www.readbyqxmd.com/read/29232612/aliphatic-hydrocarbons-recovered-in-vegetables-from-soils-based-on-their-in-situ-distribution-in-various-soil-humus-fractions-using-a-successive-extraction-method
#14
Juan Zhang, Shu-Kai Fan, Ming-Hua Zhang, Michael L Grieneisen, Jian-Feng Zhang
Aliphatic hydrocarbons (AHs) are major petroleum contaminants in the environment. In this study, the AHs bound to various soil endogenetic humus fractions were separated through successive extraction. Most of the AHs (46.1%) in soils were adsorbed onto/into humic acids (HA) and a small quantity of AHs (9.6%) were organic solvent extractable. AHs in B. chinensis were also analyzed since their potential risks to the residents through ingestion. AHs from C21 to C34, so called high molecular weight AHs (HMWAHs), were dominant AHs in B...
December 6, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29232586/synthesis-and-biological-evaluation-of-coumarin-derivatives-containing-imidazole-skeleton-as-potential-antibacterial-agents
#15
Yang Hu, Yufeng Shen, Xiaohu Wu, Xiao Tu, Gao-Xue Wang
Emergence of multidrug-resistant bacteria causes an urgent need for new generation of antibiotics, which may have a different mechanism of inhibition or killing action from the existing. Here, we report on the design, synthesis, and biological evaluation of thirty-nine coumarin derivatives in order to solve the antibacterial resistance by targeting at the inhibition of biosynthesis pathway of fatty acids. Their antibacterial activities against Escherichia coli, Staphylococcus aureus, Streptococcus agalactiae, and Flavobacterium cloumnare are tested and action mechanism against the key enzyme in bacterial fatty acid synthesis pathway are studied...
December 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29232583/development-of-novel-bis-pyrazole-derivatives-as-antitumor-agents-with-potent-apoptosis-induction-effects-and-dna-damage
#16
Hong Dai, Shushan Ge, Jing Guo, Shi Chen, Meiling Huang, Jiaying Yang, Siyu Sun, Yong Ling, Yujun Shi
A series of bis-pyrazole derivatives were designed and synthesized, and their antitumor effects in vitro and in vivo were investigated. Several compounds displayed good antiproliferative activity with IC50 values in low-micromolar range against three human cancer cell lines in vitro, superior to 5-FU. The most potent compound 10M selectively inhibited human hepatocellular carcinoma cells but not non-tumor liver cell proliferation in vitro, and significantly triggered SMMC-7721 cell apoptosis by cleavage of both PARP and caspase-3 in a concentration-dependent manner...
December 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29232580/design-and-synthesis-of-novel-quinacrine-1-3-thiazinan-4-one-hybrids-for-their-anti-breast-cancer-activity
#17
V Raja Solomon, Sheetal Pundir, Hoang-Thanh Le, Hoyun Lee
In an attempt to develop effective and safe anticancer agents, we designed, synthesized and examined 23 novel quinacrine (QC) derivatives by combining the 9-aminoacridine scaffold and the [1,3]thiazinan-4-ones group. Most of these hybrids showed strong anticancer activities, among which 3-(3-(6-chloro-2-methoxyacridin-9-ylamino)propyl)-2-(thiophen-2-yl)-1,3-thiazinan-4-one (25; VR151) effectively killed many different cancer cell types, including eight breast cancer cell lines with different genetic background, two prostate cancer and two lung cancer cell lines...
December 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29232579/structure-based-identification-of-a-nedd8-activating-enzyme-inhibitor-via-drug-repurposing
#18
Ke-Jia Wu, Hai-Jing Zhong, Guodong Li, Chenfu Liu, Hui-Min David Wang, Dik-Lung Ma, Chung-Hang Leung
NEDD8-activating enzyme (NAE) is an essential player of the NEDD8 conjugation pathway that regulates protein degradation. Meanwhile, drug repurposing is a cost-efficient strategy to identify new therapeutic uses for existing scaffolds. In this report, mitoxantrone (1) was repurposed as an inhibitor of NAE by virtual screening of an FDA-approved drug database. Compound 1 inhibited NAE activity in cell-free and cell-based systems with high selectivity and was competitive with ATP. Furthermore, compound 1 induced apoptosis of colorectal adenocarcinoma cancer cells through inhibiting the degradation of the neddylation substrate p53...
December 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29232577/attachment-and-motivational-systems-relevance-of-sensitivity-to-punishment-for-eating-disorder-psychopathology
#19
Alessio Maria Monteleone, Valentina Cardi, Umberto Volpe, Giovanna Fico, Valeria Ruzzi, Francesca Pellegrino, Giovanni Castellini, Palmiero Monteleone, Mario Maj
An altered balance of reward and inhibition systems may explain Eating Disorder (ED) behaviors and could be related to difficulties in socio-emotional processing. According to attachment theory, early interaction with caregivers affects the ability to regulate emotion in adult interpersonal situation. The aim of our study was to investigate if insecure attachment may be related to ED symptomatology through changes in reward and inhibition systems. Seventy-eight people affected by EDs and 45 healthy controls (HC) filled in the Attachment Style Questionnaire (ASQ), the Behavioral Inhibition System-Behavioral Activation System Scale (BIS-BAS) and the Eating Disorders Inventory-2 (EDI-2) questionnaire...
December 5, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/29232559/cilostazol-a-phosphodiesterase-3-inhibitor-activates-proteasome-proteolysis-and-attenuates-tauopathy-and-cognitive-decline
#20
Ari W Schaler, Natura Myeku
Alzheimer's disease and several variants of frontotemporal degeneration including progressive supranuclear palsy and corticobasal degeneration are characterized by the accumulation of abnormal tau protein into aggregates. Most proteins, including tau, are degraded via the ubiquitin proteasome system, but when abnormal tau accumulates, the function of 26S proteasomes is downregulated. The negative effect of tau aggregates on the function of the proteasome can have deleterious consequences on protein homeostasis and disease progression...
November 23, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
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