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https://www.readbyqxmd.com/read/28454210/statins-and-pancreatic-cancer
#1
Jun Gong, Esha Sachdev, Lori A Robbins, Emily Lin, Andrew E Hendifar, Monica M Mita
Pancreatic cancer remains among the most lethal cancers, despite ongoing advances in treatment for all stages of the disease. Disease prevention represents another opportunity to improve patient outcome, with metabolic syndrome and its components, such as diabetes, obesity and dyslipidemia, having been recognized as modifiable risk factors for pancreatic cancer. In addition, statins have been shown to potentially reduce pancreatic cancer risk and to improve survival in patients with a combination of metabolic syndrome and pancreatic cancer...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454041/long-term-intake-of-a-high-protein-diet-increases-liver-triacylglycerol-deposition-pathways-and-hepatic-signs-of-injury-in-rats
#2
Rubén Díaz-Rúa, Jaap Keijer, Andreu Palou, Evert M van Schothorst, Paula Oliver
Intake of high-protein (HP) diets has increased over the last years, mainly due to their popularity for body weight control. Liver is the main organ handling ingested macronutrients and it is associated with the beginning of different pathologies. We aimed to deepen our knowledge on molecular pathways affected by long-term intake of an HP diet. We performed a transcriptome analysis on liver of rats chronically fed with a casein-rich HP diet and analyzed molecular parameters related to liver injury. Chronic increase in the dietary protein/carbohydrate ratio up-regulated processes related with amino acid uptake/metabolism and lipid synthesis, promoting a molecular environment indicative of hepatic triacylglycerol (TG) deposition...
April 19, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28453664/glycogen-synthesis-in-glycogenin-1-deficient-patients-a-role-for-glycogenin-2-in-muscle
#3
Thomas O Krag, Cristina Ruiz Ruiz, John Vissing
Context: Glycogen storage disease type XV (GSD XV) is a rare disease caused by mutations in the GYG1 gene that codes for the core molecule of muscle glycogen, glycogenin 1. Nonetheless, glycogen is present in muscles of glycogenin 1 deficient patients, suggesting an alternative for glycogen build-up. A likely candidate is glycogenin 2, an isoform expressed in liver and heart, but not in healthy skeletal muscle. Objective: We wanted to investigate the formation of glycogen and changes in glycogen metabolism in patients with GSD XV...
April 27, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28453527/altered-nucleocytoplasmic-proteome-and-transcriptome-distributions-in-an-in-vitro-model-of-amyotrophic-lateral-sclerosis
#4
Jee-Eun Kim, Yoon Ho Hong, Jin Young Kim, Gye Sun Jeon, Jung Hee Jung, Byung-Nam Yoon, Sung-Yeon Son, Kwang-Woo Lee, Jong-Il Kim, Jung-Joon Sung
Aberrant nucleocytoplasmic localization of proteins has been implicated in many neurodegenerative diseases. Evidence suggests that cytoplasmic mislocalization of nuclear proteins such as transactive response DNA-binding protein 43 (TDP-43) and fused in sarcoma (FUS) may be associated with neurotoxicity in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. This study investigated the changes in nucleocytoplasmic distributions of the proteome and transcriptome in an in vitro model of ALS...
2017: PloS One
https://www.readbyqxmd.com/read/28449558/in-silicomodel-driven-assessment-of-the-effects-of-brain-derived-neurotrophic-factor-deficiency-on-glutamate-and-gamma-aminobutyric-acid-implications-for-understanding-schizophrenia-pathophysiology
#5
Rimjhim Agrawal, Sunil Vasu Kalmady, Ganesan Venkatasubramanian
Objective: Deficient brain-derived neurotrophic factor (BDNF) is one of the important mechanisms underlying the neuroplasticity abnormalities in schizophrenia. Aberration in BDNF signaling pathways directly or circuitously influences neurotransmitters like glutamate and gamma-aminobutyric acid (GABA). For the first time, this study attempts to construct and simulate the BDNF-neurotransmitter network in order to assess the effects of BDNF deficiency on glutamate and GABA. Methods: Using CellDesigner, we modeled BDNF interactions with calcium influx via N-methyl-D-aspartate receptor (NMDAR)- Calmodulin activation; synthesis of GABA via cell cycle regulators protein kinase B, glycogen synthase kinase and β-catenin; transportation of glutamate and GABA...
May 31, 2017: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28449327/skeletal-muscle-il-15-il-15r%C3%AE-and-myofibrillar-protein-synthesis-after-resistance-exercise
#6
Alberto Pérez-López, James McKendry, Marcos Martin-Rincon, David Morales-Alamo, Bárbara Pérez-Köhler, David Valadés, Julia Buján, Jose A L Calbet, Leigh Breen
In vitro and in vivo studies described the myokine IL-15 and its receptor IL-15Rα as anabolic/anti-atrophy agents, however the protein expression of IL-15Rα has not been measured in human skeletal muscle and data regarding IL-15 expression remain inconclusive. The purpose of the study was to determine serum and skeletal muscle IL-15 and IL-15Rα responses to resistance exercise session and to analyse their association with myofibrillar protein synthesis (MPS). Fourteen participants performed a bilateral leg resistance exercise composed of 4 sets of leg press and 4 sets of knee extension at 75% 1RM to task failure...
April 27, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28449081/the-coxiella-burnetii-type-ivb-secretion-system-t4bss-component-dota-is-released-secreted-during-infection-of-host-cells-and-during-in-vitro-growth-in-a-t4bss-dependent-manner
#7
Brandon E Luedtke, Saugata Mahapatra, Erika I Lutter, Edward I Shaw
Coxiella burnetii is a Gram-negative intracellular pathogen and is the causative agent of the zoonotic disease Q-fever. To cause disease, C. burnetii requires a functional type IVB secretion system (T4BSS) to transfer effector proteins required for the establishment and maintenance of a membrane bound parasitophorous vacuole (PV) and further modulation of host cell process. However, it is not clear how the T4BSS interacts with the PV membrane since neither a secretion pilus nor an extracellular pore forming apparatus has not been described...
April 25, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28448806/exostosin-1-is-expressed-in-human-odontoblasts
#8
Virve Pääkkönen, Stina Saraniemi, Françoise Bleicher, Zvi Nevo, Leo Tjäderhane
OBJECTIVE: Dental pulp is soft connective tissue maintaining the vitality of the tooth, while odontoblasts form the dentin. Our earlier DNA microarray analysis revealed expression of putative tumour suppressor exostosin 1 (EXT-1) in odontoblasts. EXT-1 is essential for heparan sulphate synthesis, which may play a role in the dentin mineralization. Since the absence of the functional EXT-1 causes bone tumours, expression in odontoblasts is interesting. Our aim was to analyse further the EXT-1 expression in human tooth...
April 8, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28448468/transcriptome-analysis-of-core-dinoflagellates-reveals-a-universal-bias-towards-gc-rich-codons
#9
Ernest Williams, Allen Place, Tsvetan Bachvaroff
Although dinoflagellates are a potential source of pharmaceuticals and natural products, the mechanisms for regulating and producing these compounds are largely unknown because of extensive post-transcriptional control of gene expression. One well-documented mechanism for controlling gene expression during translation is codon bias, whereby specific codons slow or even terminate protein synthesis. Approximately 10,000 annotatable genes from fifteen "core" dinoflagellate transcriptomes along a range of overall guanine and cytosine (GC) content were used for codonW analysis to determine the relative synonymous codon usage (RSCU) and the GC content at each codon position...
April 27, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28448188/effects-of-indomethacin-on-prostanoid-synthesis-and-vasomotor-responsiveness-in-endothelium-denuded-abdominal-and-thoracic-aortas-of-wistar-rats
#10
Ruth M López, Janette E López, Jorge S López, María C Castillo, Gustavo Guevara, José A Morales, Oscar A López, Jair Lozano, Enrique F Castillo
In endothelium-denuded abdominal (but not thoracic) aortas of rats, the nonselective cyclooxygenase (COX) inhibitor, indomethacin, suppressed contractions evoked by α-adrenergic agonists hypothetically mediated by prostanoids. We aimed to identify these non-endothelial-derived contractile prostanoids released by α-adrenergic receptors activation. Endothelium-denuded abdominal and thoracic aortas of Wistar rats were used for biochemical and functional analyses. Western blot analysis showed that COX-1 and COX-2 protein levels were respectively equivalent in endothelium-denuded abdominal and thoracic aortas...
2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28448128/total-chemical-synthesis-and-folding-of-all-l-and-all-d-variants-of-oncogenic-kras-g12v
#11
Adam Marc Levinson, John H McGee, Andrew G Roberts, Gardner Creech, Ting Wang, Michael T Peterson, Ronald C Hendrickson, Gregory L Verdine, Samuel J Danishefsky
The Ras proteins are essential GTPases involved in the regulation of cell proliferation and survival. Mutated oncogenic forms of Ras alter effector binding and innate GTPase activity, leading to deregulation of downstream signal transduction. Mutated forms of Ras are involved in approximately 30% of human cancers. Despite decades of effort to develop direct Ras inhibitors, Ras has long been considered 'undruggable' due to its high affinity for GTP and its lack of hydrophobic binding pockets. Herein, we report a total chemical synthesis of all-L- and all-D-amino acid biotinylated variants of oncogenic mutant KRas(G12V)...
April 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28448121/hiv-1-frameshift-rna-targeted-triazoles-inhibit-propagation-of-replication-competent-and-multi-drug-resistant-hiv-in-human-cells
#12
Thomas A Hilimire, Jeffrey M Chamberlain, Viktoriya Anokhina, Ryan P Bennett, Oliver Swart, Jason R Myers, John M Ashton, Ryan A Stewart, Aaron L Featherston, Kathleen Gates, Eric D Helms, Harold C Smith, Stephen Dewhurst, Benjamin L Miller
The HIV-1 frameshift-stimulating (FSS) RNA, a regulatory RNA of critical importance in the virus' life cycle, has been posited as a novel target for anti-HIV drug development. We report the synthesis and evaluation of triazole-containing compounds able to bind the FSS with high affinity and selectivity. Readily accessible synthetically, these compounds are less toxic than previously reported olefin congeners. We show for the first time that FSS-targeting compounds have antiviral activity against replication-competent HIV in human cells, including a highly cytopathic, multi-drug-resistant strain...
April 27, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28448089/bone-degeneration-and-its-recovery-in-smp30-gnl-knockout-mice
#13
K Nishijima, T Ohno, A Amano, Y Kishimoto, Y Kondo, A Ishigami, S Tanaka
Senescence marker protein-30 (SMP30) decreases androgen-independently with aging and is a lactone-hydrolyzing enzyme gluconolactonase (GNL) that is involved in vitamin C biosynthesis. In the present study, bone properties of SMP30/GNL knockout (KO) mice with deficiency in vitamin C synthesis were investigated to reveal the effects of SMP30/GNL and exogenous vitamin C supplementation on bone formation. Mineral content (BMC) and mineral density (BMD) of the mandible and femur of SMP30/GNL KO and wild-type mice at 2 and 3 months of age with or without vitamin C supplementation were measured by dual-energy X-ray absorptiometry...
2017: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/28447993/synthesis-of-1-2-azaborines-and-the-preparation-of-their-protein-complexes-with-t4-lysozyme-mutants
#14
Hyelee Lee, Shih-Yuan Liu
We describe a general synthesis of 1,2-azaborines using standard air-free techniques and protein complex preparation with T4 lysozyme mutants by vapor diffusion. Oxygen- and moisture-sensitive compounds are prepared and isolated under an inert atmosphere (N2) using either a vacuum gas manifold or a glove box. As an example of azaborine synthesis, we demonstrate the synthesis and purification of the volatile N-H-B-ethyl-1,2-azaborine by a five-step sequence involving distillation and column chromatography for the isolation of products...
March 25, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447748/tenascin-c-expression-and-its-associated-pathway-in-bmscs-following-co-culture-with-mechanically-stretched-ligament-fibroblasts
#15
Bing Zhao, Mengcai Hu, Huiyan Wu, Chenchen Ren, Jianshe Wang, Shihong Cui
The occurrence of pelvic organ prolapse (POP) is closely associated with alterations in the extracellular matrix proteins of the supporting ligament. Bone marrow mesenchymal stem cells (BMSCs) have the potential to differentiate into a variety of cell types, including osteoblasts, chondroblasts and adipocytes. Therefore, BMSCs have the potential to improve the clinical outcomes of POP. Tenascin‑C is a large glycoprotein that is present in the ECM and is involved in morphogenetic movements, and tissue patterning and repair...
March 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447740/calyptranthes-grandifolia-o-berg-myrtaceae-ethanolic-extract-inhibits-tnf-%C3%AE-gene-expression-and-cytokine-release-in%C3%A2-vitro
#16
Geórgia Muccillo Dexheimer, Luciana Knabben de Oliveira Becker Delving, Henrique Sulzbach de Oliveira, Vanderlei Biolchi, Márcia Inês Goettert, Adriane Pozzobon
Anti-tumor therapies based on anti-inflammatory effects have been considered in cancer treatment. Survival, proliferation and, resultantly, invasion and metastasis of tumor cells are regulated by local inflammatory mediators. Primary inflammatory cytokines, such as tumor necrosis factor (TNF), are targets for anticancer therapy. Several anti‑inflammatory agents isolated from natural products are becoming important chemopreventive and therapeutic agents for cancer. The present study aimed to investigate the expression of TNF‑α, nuclear factor‑κΒ (NF‑κΒ) and p38α mitogen-activated protein kinase (p38α) genes, associated with proliferation and inflammation in the Caco‑2 cell line treated with ethanolic and hexanic extracts of Calyptranthes grandifolia O...
March 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447345/in-vitro-microbial-protein-synthesis-ruminal-degradation-and-post-ruminal-digestibility-of-crude-protein-of-dairy-rations-containing-quebracho-tannin-extract
#17
J Castro-Montoya, E Westreicher-Kristen, A Henke, M Diaby, A Susenbeth, U Dickhoefer
This study evaluated the effects of Quebracho tannin extract (QTE) on in vitro ruminal fermentation, chemical composition of rumen microbes, ruminal degradation and intestinal digestibility of crude protein (iCPd). Three treatments were tested, the control (basal diet without QTE), the basal diet with 15 g QTE/kg dry matter (DM) and the basal diet with 30 g QTE/kg DM. The basal diet contained (g/kg DM): 339 grass silage, 317 maize silage and 344 concentrate. In vitro gas production kinetic was determined using the Hohenheim gas test (Experiment 1)...
April 26, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/28447192/rescue-of-a-wild-type-rabies-virus-from-cloned-cdna-and-assessment-of-the-proliferative-capacity-of-recombinant-viruses
#18
Qin Tian, Yifei Wang, Qiong Zhang, Jun Luo, Mingzhu Mei, Yongwen Luo, Xiaofeng Guo
Reverse genetic systems (RGS) have been widely used for fixed rabies virus (RABV) strains. However, RGS, for wild-type (wt) strains, have been seldom reported despite the value of this approach in defining the biological characteristics of these strains. In this work, we developed a wt RGS using a swine-origin RABV strain (GD-SH-01) for the first time. In order to have a better understanding of the contribution and function of individual gene on viral proliferation for wt RABV isolates, we constructed a full-length cDNA clone of GD-SH-01 and exchanged the single genes encoding RABV protein of a highly attenuated RABV strain HEP-Flury with those of the virulent strain...
April 26, 2017: Virus Genes
https://www.readbyqxmd.com/read/28446676/grass-carp-reovirus-vp41-targets-fish-mita-to-abrogate-the-ifn-response
#19
Long-Feng Lu, Shun Li, Zhao-Xi Wang, Si-Qi Du, Dan-Dan Chen, Pin Nie, Yong-An Zhang
Although fish possess an efficient interferon (IFN) system to defend against aquatic virus infection, the grass carp reovirus (GCRV) still causes hemorrhagic disease in grass carp. To date, GCRV's strategy for evading the fish IFN response is still unknown. Here, we report that the GCRV VP41 inhibits fish IFN production by suppressing the phosphorylation of the mediator of IRF3 activation (MITA). First, the activation of the IFN promoter (IFNpro) stimulated by the mitochondrial antiviral signaling protein (MAVS) and MITA was decreased by the overexpression of VP41, whereas such activation induced by TANK-binding kinase 1 (TBK1) was not affected...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446672/cellular-cholesterol-facilitates-the-post-entry-replication-cycle-of-herpes-simplex-virus-1
#20
George A Wudiri, Anthony V Nicola
Cholesterol is an essential component of cell membranes and is required for HSV-1 entry (1-3). Treatment of HSV-1-infected Vero cells with methyl beta-cyclodextrin from 2 - 9 hours post-entry reduced plaque numbers. Transport of incoming viral capsids to the nuclear periphery was unaffected by cholesterol reduction suggesting that cell cholesterol is important for the HSV-1 replicative cycle at a stage(s) beyond entry after the arrival of capsids at the nucleus. The synthesis and release of infectious HSV-1 and cell-to-cell spread of infection were all impaired in cholesterol-reduced cells...
April 26, 2017: Journal of Virology
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