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https://www.readbyqxmd.com/read/27922102/slc2a8-glut8-is-a-mammalian-trehalose-transporter-required-for-trehalose-induced-autophagy
#1
Allyson L Mayer, Cassandra B Higgins, Monique R Heitmeier, Thomas E Kraft, Xia Qian, Jan R Crowley, Krzysztof L Hyrc, Wandy L Beatty, Kevin E Yarasheski, Paul W Hruz, Brian J DeBosch
Trehalose is a disaccharide demonstrated to mitigate disease burden in multiple murine neurodegenerative models. We recently revealed that trehalose rapidly induces hepatic autophagy and abrogates hepatic steatosis by inhibiting hexose transport via the SLC2A family of facilitative transporters. Prior studies, however, postulate that intracellular trehalose is sufficient to induce cellular autophagy. The objective of the current study was to identify the means by which trehalose accesses the hepatocyte cytoplasm, and define the distal signaling mechanisms by which trehalose induces autophagy...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921230/upregulation-of-rock2-in-gastric-cancer-cell-promotes-tumor-cell-proliferation-metastasis-and-invasion
#2
Manhua Li, Jing Ke, Qiuhong Wang, Hongyan Qian, Lei Yang, Xunlei Zhang, Jinzhang Xiao, Haifang Ding, Xiaohang Shan, Qingqing Liu, Ying Xiao, Bojun Bao, Hua Huang
Rho-associated coiled-coil-containing protein kinase 2 (ROCK2) has been known as an effector for the small GTPase Rho and plays an important role in tumor progression and metastasis. However, the effect of ROCK2 in gastric cancer (GC) has not been identified. This study showed that ROCK2 expression significantly increased in clinical GC tissues compared with adjacent non-cancer tissues. Immunohistochemistrical analysis showed that high expression of ROCK2 was correlated with tumor grade, tumor-node-metastasis stage, infiltration depth, lymph node invasion and Ki-67, and predicted poor prognosis in 135 gastric cancer specimens...
December 5, 2016: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/27921081/a-fungus-specific-protein-domain-is-essential-for-rasa-mediated-morphogenetic-signaling-in-aspergillus-fumigatus
#3
Qusai Al Abdallah, Tiffany S Norton, Amy M Hill, Lawrence L LeClaire, Jarrod R Fortwendel
Ras proteins function as conserved regulators of eukaryotic growth and differentiation and are essential signaling proteins orchestrating virulence in pathogenic fungi. Here, we report the identification of a novel N-terminal domain of the RasA protein in the filamentous fungus Aspergillus fumigatus. Whereas this domain is absent in Ras homologs of higher eukaryotes, the N-terminal extension is conserved among fungi and is characterized by a short string of two to eight amino acids terminating in an invariant arginine...
November 2016: MSphere
https://www.readbyqxmd.com/read/27920883/exogenous-secreted-frizzled-related-protein-4-modulates-steroidogenesis-of-rat-granulosa-cells-through-wnt-%C3%AE-catenin-and-pi3k-akt-signaling-pathways
#4
Ghamartaj Hossein, Manijeh Khanmohammadi, Parisa Sahranavard Fard, Yasaman Heidarian, Somaieh Kazemnejad, Mohammad Mehdi Akhondi
BACKGROUND: It has been reported that secreted frizzled-related protein-4 known as an antagonist of Wnt signaling pathway plays a role in luteinization process of rodent granulosa cells. The purpose of this study was twofold: 1) to determine whether recombinant human secreted frizzled-related protein-4 (rhSFRP-4) could directly induce terminal differentiation of rat Granulosa Cells (GCs) and 2) to understand how the modulation of β-catenin and Protein Kinase B (PKB)/AKT activity by exogenous SFRP-4 could be involved in steroidogenesis...
October 2016: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/27920784/the-arabidopsis-angustifolia3-yoda-gene-cascade-induces-anthocyanin-accumulation-by-regulating-sucrose-levels
#5
Lai-Sheng Meng, Ying-Qiu Li, Meng-Qian Liu, Ji-Hong Jiang
Anthocyanin accumulation specifically depends on sucrose (Suc) signaling/levels. However, the gene cascades specifically involved in the Suc signaling/level-mediated anthocyanin biosynthetic pathway are still unknown. Arabidopsis ANGUSTIFOLIA3 (AN3), a transcription coactivator, is involved in the regulation of leaf shape and drought tolerance. Recently, an AN3-CONSTITUTIVE PHOTOMORPHOGENIC 1 gene cascade has been reported to regulate the light signaling-mediated anthocyanin accumulation. Target gene analysis indicates that AN3 is associated with the YODA (YDA) promoter, a mitogen-activated protein kinase kinase kinase, in vivo for inducing anthocyanin accumulation...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27920562/the-pharmacokinetics-of-vancomycin-during-the-initial-loading-dose-in-patients-with-septic-shock
#6
Wasan Katip, Sutep Jaruratanasirikul, Sutthiporn Pattharachayakul, Wibul Wongpoowarak, Arnurai Jitsurong, Aroonrut Lucksiri
OBJECTIVE: To characterize the pharmacokinetics (PK) of vancomycin in patients in the initial phase of septic shock. METHODS: Twelve patients with septic shock received an intravenous infusion of vancomycin 30 mg/kg over 2 h. The vancomycin PK study was conducted during the first 12 h of the regimen. Serum vancomycin concentration-time data were analyzed using the standard model-independent analysis and the compartment model. RESULTS: For the noncompartment analysis the mean values ± standard deviation (SD) of the estimated clearance and volume of distribution of vancomycin at steady state were 6...
2016: Infection and Drug Resistance
https://www.readbyqxmd.com/read/27920521/celastrol-nanomicelles-attenuate-cytokine-secretion-in-macrophages-and-inhibit-macrophage-induced-corneal-neovascularization-in-rats
#7
Zhanrong Li, Jingguo Li, Lei Zhu, Ying Zhang, Junjie Zhang, Lin Yao, Dan Liang, Liya Wang
The aim of the present study was to investigate the inhibitory effects of celastrol-loaded nanomicelles (CNMs) on activated macrophage-induced corneal neovascularization (CNV) in rats and cytokine secretion in macrophages. Using an angiogenesis assay in vitro, we detected the effects of CNMs on human umbilical vein endothelial cell (HUVEC) migration and invasion. In addition, the expression levels of cytokines secreted from hypoxia-induced macrophages were assessed through cytokine array analysis. The expression of hypoxia-inducible factors-1α (HIF-1α), nuclear factor-kappa B p65 (NF-κB p65), phospho-nuclear factor-kappa B p65 (phospho-NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), phospho-p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2), and phospho-ERK1/2 was analyzed by western blotting...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27920472/anti-inflammatory-effect-of-cannabinoid-agonist-win55-212-on-mouse-experimental-colitis-is-related-to-inhibition-of-p38mapk
#8
Ya-Jing Feng, Yong-Yu Li, Xu-Hong Lin, Kun Li, Ming-Hua Cao
AIM: To investigate the anti-inflammatory effect and the possible mechanisms of an agonist of cannabinoid (CB) receptors, WIN55-212-2 (WIN55), in mice with experimental colitis, so as to supply experimental evidence for its clinical use in future. METHODS: We established the colitis model in C57BL/6 mice by replacing the animals' water supply with 4% dextran sulfate sodium (DSS) for 7 consecutive days. A colitis scoring system was used to evaluate the severity of colon local lesion...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27920257/pkr-mediates-inflammatory-response-induced-by-hyperosmotic-stress
#9
Kenneth T Farabaugh, Mithu Majumder, Bo-Jhih Guan, Raul Jobava, Jing Wu, Dawid Krokowski, Xing-Huang Gao, Andrew Schuster, Michelle Longworth, Edward D Chan, Massimiliano Bianchi, Madhusudan Dey, Antonis E Koromilas, Parameswaran Ramakrishnan, Maria Hatzoglou
High extracellular osmolarity results in a switch from an adaptive to an inflammatory gene expression program. We show that hyperosmotic stress activates the protein kinase R (PKR) independently of its RNA binding domain. In turn, PKR stimulated nuclear accumulation of nuclear factor-κB (NF-κB) p65 species phosphorylated at serine-536, which was paralleled by the induction of a subset of inflammatory NF-κB p65- responsive genes including inducible nitric oxide synthase (iNOS), IL-6, and IL-1β. The PKR mediated-hyperinduction of iNOS decreased cell survival in mouse embryonic fibroblasts via mechanisms involving nitric oxide (NO) synthesis and post-translational modification of proteins...
December 5, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27920252/group-i-paks-promote-skeletal-myoblast-differentiation-in-vivo-and-in-vitro
#10
Giselle A Joseph, Min Lu, Maria Radu, Jennifer K Lee, Steven J Burden, Jonathan Chernoff, Robert S Krauss
Skeletal myogenesis is regulated by signal transduction, but the factors and mechanisms involved are not well understood. The group I Paks, Pak1 and Pak2, are related protein kinases and direct effectors of Cdc42 and Rac1. Group I Paks are ubiquitously expressed and specifically required for myoblast fusion in Drosophila We report that both Pak1 and Pak2 are activated during mammalian myoblast differentiation. One pathway of activation is initiated by N-cadherin ligation, and involves the cadherin co-receptor Cdo with its downstream effector, Cdc42...
December 5, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27919968/overexpression-of-pbk-topk-contributes-to-tumor-development-and-poor-outcome-of-esophageal-squamous-cell-carcinoma
#11
Takuma Ohashi, Shuhei Komatsu, Daisuke Ichikawa, Mahito Miyamae, Wataru Okajima, Taisuke Imamura, Jun Kiuchi, Keiji Nishibeppu, Toshiyuki Kosuga, Hirotaka Konishi, Atsushi Shiozaki, Hitoshi Fujiwara, Kazuma Okamoto, Hitoshi Tsuda, Eigo Otsuji
BACKGROUND: PDZ-binding kinase/T-cell-originated protein kinase (PBK/TOPK) is a serine-threonine kinase and overexpressed in various types of cancer. PBK/TOPK is associated with tumor cell development and progression through suppression of p53 function. In this study, we tested whether PBK acts as a cancer-promoting factor by being overexpressed in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: We analyzed PBK/TOPK expression in 15 ESCC cell lines, and 54 primary ESCC tumors that were curatively resected between 1994 and 2007...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919956/expression-patterns-of-growth-and-survival-genes-with-prognostic-implications-in-advanced-pancreatic-cancer
#12
Dimitrios Pectasides, Vasiliki Kotoula, George Papaxoinis, Zoi Alexopoulou, Christos Dervenis, Epaminontas Samantas, Kleo Papaparaskeva, Elpida Charalambous, Chrysoula Gkakou, Christos Agalianos, Konstantine T Kalogeras, George Pentheroudakis, George Fountzilas
AIM: The aim of this study was to evaluate the mRNA expression pattern of growth- and survival-related genes and assess their prognostic significance in patients with advanced pancreatic cancer. PATIENTS AND METHODS: In total, 98 patients were included in this retrospective translational research study and were evaluated for Kirsten rat sarcoma viral oncogene homolog (KRAS) mutational status, and v-akt murine thymoma viral oncogene homolog 1 (AKT1), AKT serine/threonine kinase 2 (AKT2), AKT serine/threonine kinase 3 (AKT3), cyclin D1 (CCND1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), hepatocellular growth factor receptor (MET), avian myelomatosis viral oncogene homolog (MYC), nuclear factor kappa B subunit 1 (NFKb1), phosphatase and tensin homolog (PTEN) and mechanistic target of rapamycin (FRAP1) genes mRNA expression...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919951/rho-associated-protein-kinase-rock-inhibitors-inhibit-survivin-expression-and-sensitize-pancreatic-cancer-stem-cells-to-gemcitabine
#13
Hiroyuki Takeda, Masashi Okada, Shuhei Suzuki, Kenta Kuramoto, Hirotsugu Sakaki, Hikaru Watarai, Tomomi Sanomachi, Shizuka Seino, Takashi Yoshioka, Chifumi Kitanaka
BACKGROUND: Targeting pathways regulating survivin expression, which has been implicated in multidrug resistance of cancer cells, is a promising strategy to overcome cancer chemoresistance. To date, the role of rho-associated protein kinases (ROCKs) in survivin expression remains largely unknown. MATERIALS AND METHODS: The effects of ROCK inhibitors Y-27632 and fasudil on survivin expression and cell viability were determined by immunoblot analysis and dye exclusion, respectively, in PANC-1 CSLC, a cancer stem cell line derived from a serum-cultured, gemcitabine-sensitive pancreatic cancer cell line, PANC-1...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919945/the-leloir-pathway-of-galactose-metabolism-a-novel-therapeutic-target-for-hepatocellular-carcinoma
#14
Manshu Tang, Enoabasi Etokidem, Kent Lai
Hepatocellular carcinoma (HCC) is one of the most lethal types of cancer worldwide, with poor prognosis and limited treatments. In order to identify novel therapeutic targets that will lead to development of effective therapies with manageable side effects, we tested the hypothesis that knocking-down galactokinase (GALK1) or galactose-1 phosphate uridylyltransferase (GALT) gene expression would control the growth of cultured hepatoma cells. Our results showed small interfering RNA (siRNA) against GALK1 or GALT inhibited the growth of HepG2 cells in culture...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919827/pkc%C3%AE-ii-mediated-cross-talk-of-trpv1-cb2-modulates-the-glucocorticoid-induced-osteoclast-overactivity
#15
Giulia Bellini, Marco Torella, Iolanda Manzo, Chiara Tortora, Livio Luongo, Francesca Punzo, Nicola Colacurci, Bruno Nobili, Sabatino Maione, Francesca Rossi
In this study, we investigated the role of the endovanilloid/endocannabinoid system in the glucocorticoid-induced osteoclast overactivity. Receptorial and enzymatic component of the endovanilloid/endocannabinoid system are expressed in bone cells, and dysregulated when bone mass is reduced. Moreover, blockade or desensitization of vanilloid receptor 1 (TRPV1) and/or stimulation of cannabinoid receptor 2 (CB2) are beneficial for reducing number and activity of the bone cells modulating resorption, the osteoclasts...
December 2, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27919788/ectopic-overexpression-of-filamin-c-scaffolds-mek1-2-and-erk1-2-to-promote-the-progression-of-human-hepatocellular-carcinoma
#16
Baicai Yang, Yun Liu, Jie Zhao, Kaiwen Hei, Hao Zhuang, Qiang Li, Wen Wei, Ruibing Chen, Ning Zhang, Yongmei Li
Hepatocellular carcinoma (HCC) invasion and metastasis are mediated by a complicated signal transduction network and downstream cytoskeletal and adhesion molecules. In this study, a microarray-based analysis revealed a dramatic increase in filamin C (FLNC), which is commonly expressed in muscle rather than in liver cells, in the two metastatic HCC cell lines MHCC97L and HCCLM3. Clinicopathological studies showed that increased FLNC expression was associated with microvascular invasion and poor prognosis. Specific hypomethylation was identified within the FLNC promoter region in HCC cell lines and patient tumor samples, which might contribute to the ectopic overexpression of FLNC...
December 2, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27919735/quercetin-attenuates-high-fructose-feeding-induced-atherosclerosis-by-suppressing-inflammation-and-apoptosis-via-ros-regulated-pi3k-akt-signaling-pathway
#17
Xue-Li Lu, Cui-Hua Zhao, Xin-Liang Yao, Han Zhang
Quercetin is a dietary flavonoid compound extracted from various plants, such as apple and onions. Previous studies have revealed its anti-inflammatory, anti-cancer, antioxidant and anti-apoptotic activities. This study investigated the ability of quercetin to inhibit high fructose feeding- or LPS-induced atherosclerosis through regulating oxidative stress, apoptosis and inflammation response in vivo and in vitro experiments. 50 and 100mg/kg quercetin were used in our study, showing significant inhibitory role in high fructose-induced atherosclerosis via reducing reactive oxygen species (ROS) levels, Caspase-3 activation, inflammatory cytokines releasing, the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells and collagen contents as well as modulating apoptosis- and inflammation-related proteins expression...
December 2, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27919679/regulation-of-protein-kinase-c-epsilon-and-its-age-dependence
#18
Chen Kang, Jingping Qin, Wil Osei, Keli Hu
Protein kinase C (PKC) is an important mediator in the cardioprotection of ischemic preconditioning and has been shown to translocate to mitochondria upon activation. However, little is known about the cellular signaling underlying the translocation of PKC isoforms to mitochondria and its age-dependence. The present study aimed to explore whether adenosine-induced translocation of PKCε to mitochondria is mediated by caveolin-3 and/or adenosine A2B receptor/PI3 kinase mediated signaling, and whether the mitochondrial targeting of PKCε is age-related...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27919636/adrenomedullin-and-angiotensin-ii-signaling-pathways-involved-in-the-effects-on-cerebellar-antioxidant-enzymes-activity
#19
Figueira Leticia, Israel Anita
Human adrenomedullin (AM) is a 52-amino acid peptide involved in cardiovascular control. AM has two specific receptors formed by the calcitonin-receptor-like receptor (CRLR) and receptor activity-modifying protein (RAMP) 2 or 3, known as AM1 and AM2 receptors, respectively. In addition, AM has appreciable affinity for the calcitonin gene-1 related peptide receptor (CGRP1), composed of CRLR/RAMP1. In brain, AM and their receptors are expressed in several localized areas, including the cerebellum. AM has been reported as an antioxidant...
December 2, 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27919590/rebuttal-to-the-manuscript-by-r-j-porter-epires-d-16-00150
#20
D G A Kasteleijn-Nolst Trenité
Development of new effective medicines for patients, who continue to have seizures or experience unwanted side-effects, is an important goal. The human "Photosensitivity Model", a POC study, helps to achieve this goal by providing accurate PharmacoKinetic / PharmcoDynamic (PK/PD) data in epilepsy patients at a very early stage and in a highly controlled, standardized and safe setting (in- hospital video-EEG photic stimulation tests and single-dose AED administration). All information referred to in this rebuttal is based on evidence and not on personal communication...
November 27, 2016: Epilepsy Research
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