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https://www.readbyqxmd.com/read/28431433/experimental-anterior-ischemic-optic-neuropathy-in-diabetic-mice-exhibited-severe-retinal-swelling-associated-with-vegf-elevation
#1
Ming-Hui Sun, Mohammad Ali Shariati, Yaping Joyce Liao
Purpose: Diabetes mellitus (DM) is one of the most important risk factors for nonarteritic anterior ischemic optic neuropathy (AION). In this study, we investigated for the first time the impact of experimental AION in a DM model. Methods: We induced a photochemical thrombosis model of AION after streptozotocin-induced DM and performed serial optical coherence tomography (OCT), morphometric analyses, and VEGF levels in the retina and sera. Results: Compared with non-DM animals, experimental AION in DM mice led to significantly greater retinal swelling on day 1 and worse thinning at week 3 on OCT measurements...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28431428/computational-and-in-vitro-experimental-investigation-of-intrathecal-drug-distribution-parametric-study-of-the-effect-of-injection-volume-cerebrospinal-fluid-pulsatility-and-drug-uptake
#2
Kevin M Tangen, Roxanne Leval, Ankit I Mehta, Andreas A Linninger
BACKGROUND: Intrathecal drug delivery is an attractive option to circumvent the blood-brain barrier for pain management through its increased efficacy of pain relief, reduction in adverse side effects, and cost-effectiveness. Unfortunately, there are limited guidelines for physicians to choose infusion or drug pump settings to administer therapeutic doses to specific regions of the spine or the brain. Although empiric trialing of intrathecal drugs is critical to determine the sustained side effects, currently there is no inexpensive in vitro method to guide the selection of spinal drug delivery parameters...
May 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28431362/rna-aptamer-based-electrochemical-aptasensor-for-c-reactive-protein-detection-using-functionalized-silica-microspheres-as-immunoprobes
#3
Junchun Wang, Jinjin Guo, Junjun Zhang, Wenjuan Zhang, Yuzhong Zhang
C-reactive protein (CRP) is a widely accepted biomarker of cardiovascular disease and inflammation. In this study, a RNA aptamer-based electrochemical sandwich type aptasensor for CRP detection was described using the functionalized silica microspheres as immunoprobes. Silica microspheres (Si MSs), which have good monodispersity and uniform shape, were firstly synthesized. The silica microspheres functionlized with gold nanoparticles (Au NPs) provided large surface area for immobilizing signal molecules (Zinc ions, Zn(2+)) and antibodies (Ab)...
April 13, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28431342/discovery-of-tetrahydrocarbazoles-as-dual-perk-and-prb-inhibitors
#4
Mahesh R Kulkarni, Madhav S Mane, Usha Ghosh, Rajiv Sharma, Nitin P Lad, Ankita Srivastava, Asha Kulkarni-Almeida, Prashant S Kharkar, Vijay M Khedkar, Shivaji S Pandit
The extracellular signal-regulated kinase (ERK) is one of the most important molecular targets for cancer that controls diverse cellular processes such as proliferation, survival, differentiation and motility. Similarly, the Rb (retinoblastoma protein) is a tumor suppressor protein and its function is to prevent excessive cell growth by inhibiting cell cycle progression. When the cell is ready to divide, pRb is phosphorylated, becomes inactive and allows cell cycle progression. Herein, we discovered a new series of tetrahydrocarbazoles as dual inhibitors of pERK and pRb phosphorylation...
March 2, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28431341/eco-friendly-synthesis-of-novel-cyanopyridine-derivatives-and-their-anticancer-and-pim-1-kinase-inhibitory-activities
#5
Khaled A M Abouzid, Ghada H Al-Ansary, Abeer M El-Naggar
Targeting Pim-1 kinase recently proved to be profitable for conquering cancer proliferation. In the current study, we report the design, synthesis and biological evaluation of two novel series of 2-amino cyanopyridine series (5a-g) and 2-oxocyanopyridine series (6a-g) targeting Pim-1 kinase. All of the newly synthesized compounds were evaluated for their in vitro anticancer activity against a panel of three cell lines, namely, the liver cancer cell line (HepG2), the colon cancer cell line (HCT-116) and the breast cancer cell line (MCF-7)...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28431319/response-of-plasma-glucagon-like-peptide-2-to-feeding-pattern-and-intraruminal-administration-of-volatile-fatty-acids-in-sheep
#6
M Elsabagh, Y Inabu, T Obitsu, T Sugino
Glucagon-like peptide-2 (GLP-2), a gut peptide secreted by enteroendocrine L cells, has recently been identified as a key regulator of intestinal growth and absorptive function in ruminants. However, reports on GLP-2 secretion are few, and more information regarding its secretion dynamics is needed. In this study, two experiments were conducted to elucidate the daily rhythm of GLP-2 secretion in response to feeding regimen and to investigate the effect of volatile fatty acids (VFA) on GLP-2 release in sheep...
March 11, 2017: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/28431311/the-low-lying-electronic-states-and-optical-schemes-for-the-laser-cooling-of-the-bh-and-bh-ions
#7
Qing-Qing Zhang, Chuan-Lu Yang, Mei-Shan Wang, Xiao-Guang Ma, Wen-Wang Liu
The potential energy curves and transition dipole moments for the 1(2)Σ(+), 2(2)Σ(+), 1(2)Π and 2(2)Π electronic states of the two molecules are calculated using multi-reference configuration interaction and the large basis sets aug-cc-pwCV5Z. Based on the obtained potential energy curves, the rotational and vibrational energy levels of the states are obtained by solving the Schrödinger equation of nuclear motion, and the spectroscopic parameters are then obtained by fitting the energy levels to Dunham series expansions...
April 9, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28431259/allosteric-regulation-of-metabolism-in-cancer-endogenous-mechanisms-and-considerations-for-drug-design
#8
REVIEW
Jamie A Macpherson, Dimitrios Anastasiou
Alterations in metabolic processes have been linked to various diseases, including cancer. Although gene expression can dictate long-term metabolic adaptation, many metabolic changes found in cancer are associated with altered allosteric properties of the underlying enzymes. Small molecule-protein interactions and intracellular signalling converge to orchestrate these allosteric mechanisms, which, emerging evidence suggests, constitute a promising therapeutic avenue. In this review we focus on glucose and energy metabolism to illustrate the role of allostery in cancer physiology and we discuss approaches to streamline the process of targeting aberrant allosteric pathways with small molecules...
April 18, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28431241/akt-pkb-signaling-navigating-the-network
#9
REVIEW
Brendan D Manning, Alex Toker
The Ser and Thr kinase AKT, also known as protein kinase B (PKB), was discovered 25 years ago and has been the focus of tens of thousands of studies in diverse fields of biology and medicine. There have been many advances in our knowledge of the upstream regulatory inputs into AKT, key multifunctional downstream signaling nodes (GSK3, FoxO, mTORC1), which greatly expand the functional repertoire of AKT, and the complex circuitry of this dynamically branching and looping signaling network that is ubiquitous to nearly every cell in our body...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28431213/genome-mining-unearths-a-hybrid-nonribosomal-peptide-synthetase-like-pteridine-synthase-biosynthetic-gene-cluster
#10
Hyun Bong Park, Corey E Perez, Karl W Barber, Jesse Rinehart, Jason M Crawford
Nonribosomal peptides represent a large class of metabolites with pharmaceutical relevance. Pteridines, such as pterins, folates, and flavins, are heterocyclic metabolites that often serve as redox-active cofactors. The biosynthetic machineries for construction of these distinct classes of small molecules operate independently in the cell. Here, we discovered an unprecedented nonribosomal peptide synthetase-like-pteridine synthase hybrid biosynthetic gene cluster in Photorhabdus luminescens using genome synteny analysis...
March 15, 2017: ELife
https://www.readbyqxmd.com/read/28431209/drug-delivery-systems-based-on-hydroxyethyl-starch
#11
Constantinos M Paleos, Zili Sideratou, Dimitris Tsiourvas
Τhe advantageous biological properties of hydroxyethyl starch (HES) triggered research interest towards design and synthesis of Drug Delivery Systems (DDSs) based on this polysaccharide. Convenient reaction schemes, including one-step reactions, led to the synthesis of HES conjugates with selected anticancer molecules or therapeutic proteins. Nanocapsules and hydrogels based on HES were also prepared and studied as prospective drug delivery systems. Formulations originating from these drug conjugates and also from nanocapsules and hydrogels loaded with drugs were characterized, highlighting on the extension of their half-life in plasma which is a critical property as far as their efficacy is concerned...
April 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28431183/efficacy-of-tiamulin-alone-or-in-combination-with-chlortetracycline-against-experimental-mycoplasma-gallisepticum-infection-in-chickens
#12
A Garmyn, M Vereecken, K Degussem, W Depondt, F Haesebrouck, A Martel
Mycoplasma gallisepticum (M. gallisepticum) remains one of the most important diseases in poultry production. Controlling the impact of the disease is done by eradication of positive breeder flocks or by vaccination and medication. A widely used molecule in medication programs is tiamulin, a pleuromutilin antibiotic. Since recent data on the in vivo efficacy of this molecule are scarce, 2 challenge studies were conducted using a recently isolated M. gallisepticum strain belonging to the wildtype population with regard to its tiamulin and tetracycline minimum inhibitory concentration (MIC)...
April 20, 2017: Poultry Science
https://www.readbyqxmd.com/read/28431169/spa-ln-a-scoring-function-of-ligand-nucleic-acid-interactions-via-optimizing-both-specificity-and-affinity
#13
Zhiqiang Yan, Jin Wang
Nucleic acids have been widely recognized as potential targets in drug discovery and aptamer selection. Quantifying the interactions between small molecules and nucleic acids is critical to discover lead compounds and design novel aptamers. Scoring function is normally employed to quantify the interactions in structure-based virtual screening. However, the predictive power of nucleic acid-ligand scoring functions is still a challenge compared to other types of biomolecular recognition. With the rapid growth of experimentally determined nucleic acid-ligand complex structures, in this work, we develop a knowledge-based scoring function of nucleic acid-ligand interactions, namely SPA-LN...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28431025/1h-magnetic-resonance-spectroscopy-of-live-human-sperm
#14
S Reynolds, S J Calvert, M N Paley, A A Pacey
STUDY QUESTION: Can 1H Magnetic Resonance Spectroscopy (MRS) be used to obtain information about the molecules and metabolites in live human spermatozoa? SUMMARY ANSWER: Percoll-based density gradient centrifugation (DGC) followed by a further two washing steps, yielded enough sperm with minimal contamination (<0.01%) from seminal fluid to permit effective MRS which detected significant differences (p < 0.05) in the choline/glycerophosphocholine, lipid and lactate regions of the 1H MRS spectrum between sperm in the pellet and those from the 40/80% interface...
April 18, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28430987/rab32-subfamily-small-gtpases-pleiotropic-rabs-in-endosomal-trafficking
#15
Norihiko Ohbayashi, Mitsunori Fukuda, Yasunori Kanaho
Rab small GTPases, well-known regulators of membrane trafficking pathways in eukaryotic cells, comprise approximately 60 different members in mammals. During the past decade, our understanding of the functions of mammalian Rab32 subfamily members (Rab32 and Rab38) have deepened, especially on the biogenesis of lysosome-related organelles, such as melanosomes, and the protection mechanisms against several pathogenic microbial infections. Endosome-mediated membrane trafficking by Rab32 subfamily members plays pivotal roles in these events...
April 14, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28430982/evidence-of-nuclei-encoded-spliceosome-mediating-splicing-of-mitochondrial-rna
#16
Roberto H Herai, Priscilla D Negraes, Alysson R Muotri
Mitochondria are thought to have originated as free-living prokaryotes. Mitochondria organelles have small circular genomes with substantial structural (absence of histones and introns) and genetic similarity to bacteria. Contrary to the prevailing concept of intronless mitochondria, here we present evidences that mitochondrial RNA transcripts (mtRNA) are not limited to policystronic molecules, but also processed as nuclei-like transcripts that are differentially spliced and expressed in a cell-type specific manner...
April 19, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28430857/repurposed-drugs-targeting-eif2%C3%AE-p-mediated-translational-repression-prevent-neurodegeneration-in-mice
#17
Mark Halliday, Helois Radford, Karlijn A M Zents, Collin Molloy, Julie A Moreno, Nicholas C Verity, Ewan Smith, Catharine A Ortori, David A Barrett, Martin Bushell, Giovanna R Mallucci
Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells. This pathway is overactivated in brains of patients with Alzheimer's disease and related disorders and has recently emerged as a promising therapeutic target for these currently untreatable conditions. Thus, in mouse models of neurodegenerative disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of protein synthesis, leading to memory impairment and neuronal loss...
April 19, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28430789/mir-9-3p-augments-apoptosis-induced-by-h2o2-through-down-regulation-of-herpud1-in-glioma
#18
Ling Yang, Yongping Mu, Hongwei Cui, Yabing Liang, Xiulan Su
MicroRNAs are short, single-stranded non-coding RNA molecules that function as regulators of tumor progression in various cancers, including glioma. The present study sought to investigate the biological functions of miR-9-3p in glioma progression. The results of a microRNA microarray indicated that microRNA-9-3p (miR-9-3p, miR-9*) is down-regulated in high-grade (grades III and IV) gliomas compared with non-tumor tissues. These results were confirmed with real-time PCR. The miR-9-3p expression level was associated with age and tumor grade...
2017: PloS One
https://www.readbyqxmd.com/read/28430714/ultrasound-molecular-imaging-of-inflammation-in-mouse-abdominal-aorta
#19
Shiying Wang, Sunil Unnikrishnan, Elizabeth B Herbst, Alexander L Klibanov, Frank William Mauldin, John A Hossack
OBJECTIVES: The aim of this study was to demonstrate a new clinically translatable ultrasound molecular imaging approach, modulated acoustic radiation force-based imaging, which is capable of rapid and reliable detection of inflammation as validated in mouse abdominal aorta. MATERIALS AND METHODS: Animal studies were approved by the Institutional Animal Care and Use Committee at the University of Virginia. C57BL/6 mice stimulated with tumor necrosis factor α, or fed with a high-fat diet, were used as inflammation (MInflammation) and diet-induced obesity (DIO) (MDIO) models, respectively...
April 20, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28430696/sequential-analysis-of-a-panel-of-biomarkers-and-pathologic-findings-in-a-resuscitated-rat-model-of-sepsis-and-recovery
#20
Nishkantha Arulkumaran, Marije L Sixma, Elisa Jentho, Elias Ceravola, Paul S Bass, John A Kellum, Robert J Unwin, Fred W K Tam, Mervyn Singer
OBJECTIVES: To characterize the temporal pattern of a panel of blood and urinary biomarkers in an animal model of fecal peritonitis and recovery. DESIGN: Prospective observational animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: A fluid-resuscitated, long-term (3 d) rat model of sepsis (fecal peritonitis) and recovery was used to understand the temporal association of sepsis biomarkers in relation to systemic hemodynamics, inflammation, and renal function...
April 20, 2017: Critical Care Medicine
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