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https://www.readbyqxmd.com/read/29453094/a-multidisciplinary-study-of-3-%C3%AE-d-glucopyranosyl-5-substituted-1-2-4-triazole-derivatives-as-glycogen-phosphorylase-inhibitors-computation-synthesis-crystallography-and-kinetics-reveal-new-potent-inhibitors
#1
Sándor Kun, Jaida Begum, Efthimios Kyriakis, Evgenia C V Stamati, Thomas A Barkas, Eszter Szennyes, Éva Bokor, Katalin E Szabó, George A Stravodimos, Ádám Sipos, Tibor Docsa, Pál Gergely, Colin Moffatt, Myrto S Patraskaki, Maria C Kokolaki, Alkistis Gkerdi, Vassiliki T Skamnaki, Demetres D Leonidas, László Somsák, Joseph M Hayes
3-(β-d-Glucopyranosyl)-5-substituted-1,2,4-triazoles have been revealed as an effective scaffold for the development of potent glycogen phosphorylase (GP) inhibitors but with the potency very sensitive to the nature of the alkyl/aryl 5-substituent (Kun et al., Eur. J. Med. Chem. 2014, 76, 567). For a training set of these ligands, quantum mechanics-polarized ligand docking (QM-PLD) demonstrated good potential to identify larger differences in potencies (predictive index PI = 0.82) and potent inhibitors with K i 's < 10 μM (AU-ROC = 0...
February 2, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29443777/oral-leukoplakia-a-precancerous-lesion-of-squamous-cell-carcinoma-in-patients-with-long-term-pegylated-liposomal-doxorubicin-treatment
#2
Hidetaka Nomura, Kimihiko Sakamoto, Takeru Sugihara, Shuhei Okamoto, Yoichi Aoki, Terumi Tanigawa, Maki Matoda, Kohei Omatsu, Hiroyuki Kanao, Kazuyoshi Kato, Kuniko Utsugi, Yuko Sugiyama, Nobuhiro Takeshima
Pegylated liposomal doxorubicin (PLD) has a good safety profile, but long-term use has been associated with development of squamous cell carcinoma of the tongue and oral cavity (SCCTO) in some patients. The study objective was to estimate the prevalence of oral leukoplakia, a known precursor of SCCTO, in patients with ovarian cancer and long-term PLD use.After approval of the institutional review board, medical record of 114 patients who were treated with PLD at our institution between January 2010 and December 2016 were retrospectively reviewed...
February 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29438048/hydrogen-sulfide-increases-production-of-nadph-oxidase-dependent-hydrogen-peroxide-and-phospholipase-d-derived-phosphatidic-acid-in-guard-cell-signaling
#3
Denise Scuffi, Thomas Nietzel, Luciano Di Fino, Andreas J Meyer, Lorenzo Lamattina, Markus Schwarzländer, Ana M Laxalt, Carlos Garcia-Mata
Hydrogen sulfide (H2S) has emerged as an important gaseous signaling molecule in plants participating in several stresses and developmental processes. L-cysteine desulfhydrase 1 (DES1), one of the enzymatic sources of H2S in plants, was shown to participate in ABA-induced stomatal closure. In this work we combined pharmacological and genetic approaches to elucidate the involvement of H2S in stomatal closure and the interplay between H2S and other second messengers of the guard cell signaling network, such as hydrogen peroxide (H2O2) and phospholipase D (PLD)-derived phosphatidic acid (PA) in Arabidopsis...
February 2, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29435317/impact-of-liver-volume-on-polycystic-liver-disease-related-symptoms-and-quality-of-life
#4
Myrte K Neijenhuis, Wietske Kievit, Stef Mh Verheesen, Hedwig M D'Agnolo, Tom Jg Gevers, Joost Ph Drenth
Background: Symptoms in polycystic liver disease (PLD) are thought to be caused by compression of organs and structures by the enlarged liver. Aim: The aim of this article is to assess the impact of liver volume on symptoms and quality of life (QoL) in PLD. Methods: We included PLD patients from two prospective studies that used the PLD-questionnaire (PLD-Q) for symptom assessment. QoL was assessed through SF-36, summarized in a physical (PCS) and mental (MCS) component score...
February 2018: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/29433083/inhibition-of-phospholipases-influences-the-metabolism-of-wound-induced-benzylisoquinoline-alkaloids-in-papaver-somniferum-l
#5
Veronika Jablonická, Jörg Ziegler, Zuzana Vatehová, Desana Lišková, Ingo Heilmann, Marek Obložinský, Mareike Heilmann
Benzylisoquinoline alkaloids (BIAs) are important secondary plant metabolites and include medicinally relevant drugs, such as morphine or codeine. As the de novo synthesis of BIA backbones is (still) unfeasible, to date the opium poppy plant Papaver somniferum L. represents the main source of BIAs. The formation of BIAs is induced in poppy plants by stress conditions, such as wounding or salt treatment; however, the details about regulatory processes controlling BIA formation in opium poppy are not well studied...
January 31, 2018: Journal of Plant Physiology
https://www.readbyqxmd.com/read/29429842/trabectedin-in-ovarian-cancer-is-it-now-a-standard-of-care
#6
J Ventriglia, I Paciolla, S C Cecere, C Pisano, M Di Napoli, L Arenare, S V Setola, N S Losito, D Califano, M Orditura, S Pignata
In patients with recurrent ovarian cancer, the choice of second-line therapy is complex. Several factors have to be considered, such as platinum-free interval (PFI), residual toxicity from the previous treatments, BRCA1/2 gene mutation status. Trebectedin is a minor groove DNA binder derived from a marine organism that has shown efficacy in different settings in ovarian cancer therapy. It has been approved in the treatment of partially platinum sensitive (PPS) (PFI between 6 and 12 months) relapsed ovarian cancer according to the statistically significant progression-free survival (7...
February 8, 2018: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/29413587/targeting-the-leptin-receptor-to-evaluate-therapeutic-efficacy-and-anti-tumor-effects-of-doxil-in-vitro-and-in-vivo-in-mice-bearing-c26-colon-carcinoma-tumor
#7
Shahrzad Amiri Darban, Sara Nikoofal-Sahlabadi, Nafise Amiri, Nafiseh Kiamanesh, Amin Mehrabian, Bamdad Zendehbad, Zahra Gholizadeh, Mahmoud Reza Jaafari
Leptin is an appetite regulatory hormone that is secreted into the blood circulation by the adipose tissue and it functions via its over expressed receptors (Ob-R) in a wide variety of cancers. In the present study, the function of a leptin-derived peptide (LP16, 91-110 of Leptin) was investigated as a targeting ligand to decorate PEGylated liposomal doxorubicin (PLD, Doxil®) surface and the anti-tumor activity and therapeutic efficacy of Doxil in C26 (Colon Carcinoma) tumor model were also evaluated. As a result of this, Doxil with different LP16 peptide density (25, 50, 100 and 200 peptide on the surface of each liposome) was successfully prepared and characterized...
January 26, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29401246/anti-napi2b-antibody-drug-conjugate-lifastuzumab-vedotin-dnib0600a-compared-to-pegylated-liposomal-doxorubicin-in-patients-with-platinum-resistant-ovarian-cancer-in-a-randomized-open-label-phase-ii-study
#8
S Banerjee, A M Oza, M J Birrer, E P Hamilton, J Hasan, A Leary, K N Moore, B Mackowiak-Matejczyk, J Pikiel, I Ray-Coquard, P Trask, K Lin, E Schuth, A Vaze, Y Choi, J C Marsters, D J Maslyar, V Lemahieu, Y Wang, E W Humke, J F Liu
Background: Lifastuzumab vedotin (LIFA) is a humanized anti-NaPi2b monoclonal antibody conjugated to a potent anti-mitotic agent, monomethyl auristatin E (MMAE), which inhibits cell division by blocking the polymerization of tubulin. This study is the first to compare an antibody-drug-conjugate (ADC) to standard-of-care in ovarian cancer (OC) patients. Patients and Methods: Platinum-resistant OC patients were randomized to receive LIFA (2.4 mg/kg, intravenously, every 3 weeks [Q3W]), or pegylated liposomal doxorubicin (PLD) (40 mg/m2, intravenously, Q4W)...
February 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29386256/phospholipase-d-in-tcr-mediated-signaling-and-t-cell-activation
#9
Minghua Zhu, Daniel P Foreman, Sarah A O'Brien, Yuefei Jin, Weiguo Zhang
Phospholipase D (PLD) is an enzyme that catalyzes the hydrolysis of phosphatidylcholine, the major phospholipid in the plasma membrane, to generate an important signaling lipid, phosphatidic acid. Phosphatidic acid is a second messenger that regulates vesicular trafficking, cytoskeletal reorganization, and cell signaling in immune cells and other cell types. Published studies, using pharmacological inhibitors or protein overexpression, indicate that PLD plays a positive role in TCR-mediated signaling and cell activation...
January 31, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29383277/perilunate-dislocations-and-perilunate-fracture-dislocations-in-the-u-s-military
#10
John C Dunn, Logan R Koehler, Nicholas A Kusnezov, Elizabeth Polfer, Justin D Orr, Miguel A Pirela-Cruz, Justin S Mitchell
Background Perilunate dislocations and perilunate fracture dislocations (PLDs/PLFDs) are rare and often associated with poor outcomes. Heretofore, these outcomes have not been evaluated in a high-demand military population. Questions/Purpose The purpose of this study was to evaluate the outcomes in a young, active population after sustaining PLD/PLFD injuries. Patients and Methods We retrospectively reviewed the U.S. military service members who underwent surgical treatment for a PLD/PLFD (Current Procedural Terminology codes 25695 and 25685) between June 1, 2010, and June 1, 2014 through the Military Health System Management Analysis and Reporting Tool (M2) database, capturing patients with a minimum 2-year follow-up...
February 2018: Journal of Wrist Surgery
https://www.readbyqxmd.com/read/29372396/symptom-management-the-utility-of-regional-cooling-for-hand-foot-syndrome-induced-by-pegylated-liposomal-doxorubicin-in-ovarian-cancer
#11
Seiko Bun, Mayu Yunokawa, Yoshiko Tamaki, Akihiko Shimomura, Tatsunori Shimoi, Makoto Kodaira, Chikako Shimizu, Kan Yonemori, Yasuhiro Fujiwara, Yoshinori Makino, Hiroyuki Terakado, Kenji Tamura
PURPOSE: Hand-foot syndrome (HFS) is a major side effect of pegylated liposomal doxorubicin (PLD). Regional cooling during PLD infusion was shown to improve severe HFS. We investigated the utility of frozen gloves and socks (FGS) as a simpler cooling method. METHODS: To evaluate the utility and safety of regional cooling with FGS for PLD-induced HFS, we retrospectively analyzed patients with advanced ovarian cancer who used FGS during PLD-containing regimens. RESULTS: Ninety-six patients were analyzed...
January 25, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29370084/a-systematic-study-on-the-structural-and-optical-properties-of-vertically-aligned-zinc-oxide-nanorods-grown-by-high-pressure-assisted-pulsed-laser-deposition-technique
#12
Priyanka Karnati, Ariful Haque, M F N Taufique, Kartik Ghosh
In this study, we synthesize high quality vertically aligned ZnO (VAZO) nanorods on silicon, sapphire, and indium tin oxide (ITO) substrates by using pulsed laser deposition (PLD) technique at high growth pressure (0.3 Torr). Systematic changes in structural and optical properties of VAZO nanorods are studied by varying the substrate temperature (500-600 °C) and number of pulsed laser shots during the deposition. ZnO nanoparticles deposited at high pressure act as nucleation sites, eliminating requirement of catalyst to fabricate VAZO nanorods...
January 25, 2018: Nanomaterials
https://www.readbyqxmd.com/read/29366679/the-combination-of-an-hdac6-inhibitor-and-a-somatostatin-receptor-agonist-synergistically-reduces-hepato-renal-cystogenesis-in-an-animal-model-of-polycystic-liver-disease
#13
Maria Lorenzo Pisarello, Tatyana V Masyuk, Sergio A Gradilone, Anatoliy I Masyuk, Jingyi Francess Ding, Pui-Yuen Lee, Nicholas F LaRusso
Hepatic cystogenesis in polycystic liver disease (PLD) is associated with abnormalities in multiple cellular processes, including elevated cAMP and over-expression of histone deacetylase 6 (HDAC6). Disease progression in PCK rats (an animal model of PLD) is attenuated by inhibition of either cAMP production or HDAC6. Therefore, we hypothesized that concurrent targeting of HDAC6 and cAMP would synergistically reduce cyst growth. Changes in hepato-renal cystogenesis were examined in PCK rats treated with: i) a pan-HDAC inhibitor, panobinostat; ii) three specific HDAC6 inhibitors, ACY-1215, ACY-738, and ACY-241; and iii) a combination of ACY-1215 and the somatostatin receptor analog, pasireotide...
January 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29340795/the-sesquiterpene-botrydial-from-botrytis-cinerea-induces-phosphatidic-acid-production-in-tomato-cell-suspensions
#14
Juan Martin D'Ambrosio, Gabriela Gonorazky, Daniela J Sueldo, Javier Moraga, Andrés Arruebarrena Di Palma, Lorenzo Lamattina, Isidro González Collado, Ana Maria Laxalt
The phytotoxin botrydial triggers PA production in tomato cell suspensions via PLD and PLC/DGK activation. PLC/DGK-derived PA is partially required for botrydial-induced ROS generation. Phosphatidic acid (PA) is a phospholipid second messenger involved in the induction of plant defense responses. It is generated via two distinct enzymatic pathways, either via phospholipase D (PLD) or by the sequential action of phospholipase C and diacylglycerol kinase (PLC/DGK). Botrydial is a phytotoxic sesquiterpene generated by the necrotrophic fungus Botrytis cinerea that induces diverse plant defense responses, such as the production of reactive oxygen species (ROS)...
January 16, 2018: Planta
https://www.readbyqxmd.com/read/29339469/the-bardet-biedl-syndrome-protein-complex-is-an-adapter-expanding-the-cargo-range-of-intraflagellar-transport-trains-for-ciliary-export
#15
Peiwei Liu, Karl F Lechtreck
Bardet-Biedl syndrome (BBS) is a ciliopathy resulting from defects in the BBSome, a conserved protein complex. BBSome mutations affect ciliary membrane composition, impairing cilia-based signaling. The mechanism by which the BBSome regulates ciliary membrane content remains unknown. Chlamydomonas bbs mutants lack phototaxis and accumulate phospholipase D (PLD) in the ciliary membrane. Single particle imaging revealed that PLD comigrates with BBS4 by intraflagellar transport (IFT) while IFT of PLD is abolished in bbs mutants...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29326993/turning-double-hydrophilic-into-amphiphilic-ir825-conjugated-polymeric-nanomicelles-for-near-infrared-fluorescence-imaging-guided-photothermal-cancer-therapy
#16
Guang-Yu Pan, Hao-Ran Jia, Ya-Xuan Zhu, Fu-Gen Wu
Developing biocompatible and photodegradable photothermal agents (PTAs) holds great promise for potential clinical applications in photothermal cancer therapy. Herein, a new PTA was innovatively constructed by conjugating the hydrophobic near-infrared (NIR) heptamethine cyanine molecule IR825-NH2 with a double hydrophilic block copolymer methoxypoly(ethylene glycol)5k-block-poly(l-aspartic acid sodium salt)10 (abbreviated as PEG-PLD) via amine-carboxyl reaction. The as-designed PEG-PLD(IR825) was amphiphilic and could self-assemble into polymeric nanomicelles in aqueous solutions...
January 12, 2018: Nanoscale
https://www.readbyqxmd.com/read/29324350/formation-of-phosphatidylethanol-from-endogenous-phosphatidylcholines-in-animal-tissues-from-pig-calf-and-goat
#17
Marc Luginbühl, Sytske Willem, Stefan Schürch, Wolfgang Weinmann
In the presence of alcohol, phosphatidylcholine (PC) is transformed to the direct alcohol biomarker phosphatidylethanol (PEth). This reaction is catalyzed by the enzyme phospholipase D (PLD) and dependent on substrate availability. As recent methods have solely focused on the determination of PEth, information about the PC composition was generally missing. To address this issue and monitor PC (16:0/18:1 and 16:0/18:2) and PEth (16:0/18:1 and 16:0/18:2) simultaneously, a reversed phase LC-MS/MS method based on a C8 core-shell column, coupled to a Sciex 5500 QTrap instrument was developed...
December 24, 2017: Forensic Science International
https://www.readbyqxmd.com/read/29323661/versatile-technique-for-assessing-thickness-of-2d-layered-materials-by-xps
#18
Dmitry Y Zemlyanov, Michael Jespersen, Dmitri Zakharov, Jianjun Hu, Rajib Paul, Anurag Kumar, Shanee Pacley, Nicholas Glavin, David Saenz, K C Smith, Timothy S Fisher, Andrey A Voevodin
X-ray photoelectron spectroscopy (XPS) has been utilized as a versatile method for thickness characterization of various two-dimensional (2D) films. Accurate thicknesses can be measured simultaneously while acquiring XPS data for chemical characterization for 2D film thickness up to approximately 10 nm (<10 nm). For validating the developed technique, thicknesses of few-layer graphene (FLG), MoS2 and amorphous BN layers, produced by MPCVD, PECVD, and PLD respectively, are accurately measured. The ratio between photoemission peaks recorded for the films (C 1s, Mo 3d, B1s) and the substrates (Cu 2p, Si 2p, Al 2p) is the primary input parameter for the thickness calculation, in addition to the atomic densities of the substrate and the film, and corresponding electron attenuation length...
January 11, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29318424/pasireotide-does-not-improve-efficacy-of-aspiration-sclerotherapy-in-patients-with-large-hepatic-cysts-a-randomized-controlled-trial
#19
Titus F M Wijnands, Tom J G Gevers, Marten A Lantinga, René H Te Morsche, Leo J Schultze Kool, Joost P H Drenth
OBJECTIVES: We tested whether complementary use of the somatostatin analogue pasireotide would augment efficacy of aspiration sclerotherapy of hepatic cysts. METHODS: We conducted a double-blind, placebo-controlled trial in patients who underwent aspiration sclerotherapy of a large (>5 cm) symptomatic hepatic cyst. Patients were randomized to either intramuscular injections of pasireotide 60 mg long-acting release (n = 17) or placebo (sodium chloride 0.9 %, n = 17)...
January 9, 2018: European Radiology
https://www.readbyqxmd.com/read/29311141/a-unique-homeostatic-signaling-pathway-links-synaptic-inactivity-to-postsynaptic-mtorc1
#20
Fredrick E Henry, Xiao Wang, David Serrano, Amanda S Perez, Cynthia J L Carruthers, Edward L Stuenkel, Michael A Sutton
mTORC1-dependent translational control plays a key role in several enduring forms of synaptic plasticity such as long term potentiation (LTP) and mGluR-dependent long term depression. Recent evidence demonstrates an additional role in regulating synaptic homeostasis in response to inactivity, where dendritic mTORC1 serves to modulate presynaptic function via retrograde signaling. Presently, it is unclear if LTP and homeostatic plasticity utilize a common route to mTORC1-dependent signaling or if each engage mTORC1 through distinct pathways...
January 8, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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