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https://www.readbyqxmd.com/read/29151001/intravenous-fluid-therapy-for-hospitalized-and-critically-ill-children-rationale-available-drugs-and-possible-side-effects
#1
Thomas Langer, Rosamaria Limuti, Concezione Tommasino, Niels van Regenmortel, Els L I M Duval, Pietro Caironi, Manu L N G Malbrain, Antonio Pesenti
Human beings are constituted mainly of water. In particular, children's total body water might reach 75-80% of their body weight, compared to 60-70% in adults. It is therefore not surprising, that children, especially hospitalized newborns and infants, are markedly prone to water and electrolyte imbalances. Parenteral fluid therapy is a cornerstone of medical treatment and is thus of exceptional relevance in this patient population. It is crucial to appreciate the fact that intravenous fluids are drugs with very different characteristics, different indications, contraindications and relevant side effects...
November 18, 2017: Anaesthesiology Intensive Therapy
https://www.readbyqxmd.com/read/29150954/physiological-role-of-urothelial-cancer-associated-1-long-noncoding-rna-in-human-skeletogenic-cell-differentiation
#2
Takanori Ishikawa, Takashi Nishida, Mitsuaki Ono, Takeshi Takarada, Nguyen Ha, Shinnosuke Kurihara, Takayuki Furumatsu, Yurika Murase, Masaharu Takigawa, Toshitaka Oohashi, Hiroshi Kamioka, Satoshi Kubota
A vast number of long-noncoding RNAs (lncRNA) are found expressed in human cells, which RNAs have been developed along with human evolution. However, the physiological functions of these lncRNAs remain mostly unknown. In the present study, we for the first time uncovered the fact that one of such lncRNAs plays a significant role in the differentiation of chondrocytes and, possibly, of osteoblasts differentiated from mesenchymal stem cells, which cells eventually construct the human skeleton. The urothelial cancer-associated 1 (UCA1) lncRNA is known to be associated with several human malignancies...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150749/study-on-the-interaction-of-paeoniflorin-with-human-serum-albumin-hsa-by-spectroscopic-and-molecular-docking-techniques
#3
Liang Xu, Yan-Xi Hu, Yan-Cheng Li, Yu-Feng Liu, Li Zhang, Hai-Xin Ai, Hong-Sheng Liu
The interaction of paeoniflorin with human serum albumin (HSA) was investigated using fluorescence, UV-vis absorption, circular dichroism (CD) spectra and molecular docking techniques under simulative physiological conditions. The results clarified that the fluorescence quenching of HSA by paeoniflorin was a static quenching process and energy transfer as a result of a newly formed complex (1:1). Paeoniflorin spontaneously bound to HSA in site I (subdomain IIA), which was primarily driven by hydrophobic forces and hydrogen bonds (ΔH° = - 9...
November 17, 2017: Chemistry Central Journal
https://www.readbyqxmd.com/read/29150644/therapeutic-effects-of-hepatocyte-growth-factor-overexpressing-dental-pulp-stem-cells-on-liver-cirrhosis-in-a-rat-model
#4
Xiao-Fang Cao, Shi-Zhu Jin, Liang Sun, Yuan-Bo Zhan, Feng Lin, Ying Li, Ying-Lian Zhou, Xiu-Mei Wang, Li Gao, Bin Zhang
Cirrhosis is the terminal stage of hepatic diseases and is prone to develop into hepatocyte carcinoma. Increasing evidence suggests that the transplantation of dental pulp stem cells (DPSCs) may promote recovery from cirrhosis, but the key regulatory mechanisms involved remain to be determined. In this study, we overexpressed human hepatocyte growth factor (hHGF) in primary rat DPSCs and evaluated the effects of HGF overexpression on the biological behaviors and therapeutic efficacy of grafted DPSCs in cirrhosis...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150562/the-role-of-mhc-e-in-t-cell-immunity-is-conserved-among-humans-rhesus-macaques-and-cynomolgus-macaques
#5
Helen L Wu, Roger W Wiseman, Colette M Hughes, Gabriela M Webb, Shaheed A Abdulhaqq, Benjamin N Bimber, Katherine B Hammond, Jason S Reed, Lina Gao, Benjamin J Burwitz, Justin M Greene, Fidel Ferrer, Alfred W Legasse, Michael K Axthelm, Byung S Park, Simon Brackenridge, Nicholas J Maness, Andrew J McMichael, Louis J Picker, David H O'Connor, Scott G Hansen, Jonah B Sacha
MHC-E is a highly conserved nonclassical MHC class Ib molecule that predominantly binds and presents MHC class Ia leader sequence-derived peptides for NK cell regulation. However, MHC-E also binds pathogen-derived peptide Ags for presentation to CD8(+) T cells. Given this role in adaptive immunity and its highly monomorphic nature in the human population, HLA-E is an attractive target for novel vaccine and immunotherapeutic modalities. Development of HLA-E-targeted therapies will require a physiologically relevant animal model that recapitulates HLA-E-restricted T cell biology...
November 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29150544/estimation-of-circulating-drug-metabolite-exposure-in-human-using-in-vitro-data-and-physiologically-based-pharmacokinetic-modelling-example-of-a-high-metabolite-parent-drug-ratio
#6
R Scott Obach, Jian Lin, Emi Kimoto, Sridhar Duvvuri, Timothy Nicholas, Eugene P Kadar, Larry M Tremaine, Aarti Sawant Basak
TBPT ((R)-4-((4-(((4-((tetrahydrofuran-3-yl)oxy)benzo[d]isoxazol-3-yl)oxy)methyl)piperidin-1-yl)methyl)tetrahydro-2H-pyran-4-ol), a serotonin-4 receptor partial agonist, is metabolized to two metabolites: an N-dealkylation product (M1) and a cyclized oxazolidine structure (M2). After administration to humans, the exposure to M1 was low and the exposure to M2 was high, relative to the parent drug, despite this being the opposite in vitro. In this study, projection of the plasma metabolite/parent ratios for M1 and M2 was attempted, using in vitro metabolism, binding, and permeability data in static and dynamic PBPK models...
November 17, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29150543/toxicokinetics-and-physiologically-based-pharmacokinetic-modeling-of-the-shellfish-toxin-domoic-acid-in-nonhuman-primates
#7
Jing Jing, Rebekah Petroff, Sara Shum, Brenda Crouthamel, Ariel R Topletz, Kimberly S Grant, Thomas M Burbacher, Nina Isoherranen
Domoic acid (DA), a neurotoxin, is produced by marine algae and has caused toxications worldwide in animals and humans. However, the toxicokinetics of DA has not been fully evaluated, and information is missing on the disposition of DA following oral exposures at doses that are considered safe for human consumption. In this study, toxicokinetics of DA were investigated in cynomolgus monkeys, following single doses of 5 µg/kg DA iv, 0.075 mg/kg DA po and 0.15 mg/kg DA po. Following iv dosing, DA had a systemic clearance of 124 ± 71 ml/hr/kg, volume of distribution at steady state of 131±71 ml/kg and elimination half-life of 1...
November 17, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29150437/mechanism-of-activation-of-sgk3-by-growth-factors-via-the-class-1-and-class-3-pi3ks
#8
Nazma Malik, Thomas Macartney, Annika Hornberger, Karen Anderson, Hannah Tovell, Alan R Prescott, Dario R Alessi
Derailment of the PI3K-AGC protein kinase signalling network contributes to many human diseases including cancer. Recent work has revealed that the poorly studied AGC kinase family member, SGK3 promotes resistance to cancer therapies that target the Class 1 PI3K pathway, by substituting for loss of Akt kinase activity. SGK3 is recruited and activated at endosomes, by virtue of its PX domain binding to PtdIns(3)P. Here we demonstrate that endogenous SGK3 is rapidly activated by growth factors such as IGF1, through pathways involving both Class 1 and Class 3 PI3Ks...
November 17, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29150416/-bicarbonate-from-physiology-to-treatment-for-all-clinicians
#9
Julie Beaume, Antoine Braconnier, Thibault Dolley-Hitze, Jean-Philippe Bertocchio
Acid-base regulation is essential to maintain homeostasis in humans. Carbonic acid/bicarbonate (H2CO3/HCO3(-)) couple is the most predominant extracellular buffer to keep plasma pH within a physiological range. The ability to (re)generate such a buffer is a key milestone that necessitates to understand a precise physiology of both renal tubule and digestive tract. Here, we first reviewed renal and digestive cycles of bicarbonate in physiology. We also reviewed pathological findings where acid-base disequilibrium is involved and nutritional and/or alkali therapy could be necessary...
November 14, 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/29150048/dna-dependent-protein-kinase-modulates-the-anti-cancer-properties-of-silver-nanoparticles-in-human-cancer-cells
#10
Hui Kheng Lim, Resham Lal Gurung, M Prakash Hande
Silver nanoparticles (Ag-np) were reported to be toxic to eukaryotic cells. These potentially detrimental effects of Ag-np can be advantageous in experimental therapeutics. They are currently being employed to enhance the therapeutic efficacy of cancer drugs. In this study, we demonstrate that Ag-np treatment trigger the activation of DNA-PKcs and JNK pathway at selected doses, presumably as a physiologic response to DNA damage and repair in normal and malignant cells. Ag-np altered the telomere dynamics by disrupting the shelterin complex located at the telomeres and telomere lengths...
December 2017: Mutation Research
https://www.readbyqxmd.com/read/29150005/crispr-libraries-and-screening
#11
John T Poirier
CRISPR-Cas9 technology has revolutionized large-scale functional genomic screening in mammalian cell-culture systems. Due in part to optimized lentiviral delivery vectors; it is now possible to perform CRISPR-Cas9 screens in animals in order to study biological processes in the context of a whole organism and within more physiologically relevant environment. This chapter focuses primarily on mouse models of human cancers; viral vectors used for simultaneous tumor initiation and genome editing and sgRNA library design considerations...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29149720/a-robust-strategy-for-preparation-of-sequential-stimuli-responsive-block-copolymer-prodrugs-via-thiolactone-chemistry-to-overcome-multiple-anticancer-drug-delivery-barriers
#12
Wendong Ke, Wei Yin, Zengshi Zha, Jean Felix Mukerabigwi, Weijian Chen, Yuheng Wang, Chuanxin He, Zhishen Ge
Block copolymer prodrugs (BCPs) have attracted considerable attentions in clinical translation of nanomedicine owing to their self-assembly into well-defined core-shell nanoparticles for improved pharmacokinetics, stability in blood circulation without drug leakage, and optimized biodistribution. However, a cascade of physiological barriers against specific delivery of drugs into tumor cells limit the final therapeutic efficacy. Herein, we report a robust and facile strategy based on thiolactone chemistry to fabricate well-defined BCPs with sequential tumor pH-promoted cellular internalization and intracellular stimuli-responsive drug release...
November 9, 2017: Biomaterials
https://www.readbyqxmd.com/read/29149638/roles-of-n-and-c-terminal-domains-in-the-ligand-binding-properties-of-cytoglobin
#13
Shumpei Hanai, Hirofumi Tsujino, Taku Yamashita, Ryo Torii, Hitomi Sawai, Yoshitsugu Shiro, Koji Oohora, Takashi Hayashi, Tadayuki Uno
Cytoglobin (Cygb) is a member of the hexacoordinated globin protein family and is expressed ubiquitously in rat and human tissues. Although Cygb is reportedly upregulated under hypoxic conditions both in vivo and in vitro, suggesting a physiological function to protect cells under hypoxic/ischemic conditions by scavenging reactive oxygen species or by signal transduction, the mechanisms associated with this function have not been fully elucidated. Recent studies comparing Cygbs among several species suggest that mammalian Cygbs show a distinctly longer C-terminal domain potentially involved in unique physiological functions...
November 9, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29149630/age-related-vulnerability-of-pattern-separation-in-c57bl-6j-mice
#14
Aurélia Cès, Thibaut Burg, Karine Herbeaux, Céline Héraud, Jean-Bastien Bott, Ayikoe Guy Mensah-Nyagan, Chantal Mathis
Aging is associated with impaired performance in behavioral pattern separation (PS) tasks based on similarities in object features and in object location. These deficits have been attributed to functional alterations in the dentate gyrus (DG)-CA3 region. Animal studies suggested a role of adult-born DG neurons in PS performance. The present study investigated the effect of aging in C57BL/6J mice performing PS tasks based on either object features or object location. At the age of 18 months or more, performance was severely impaired in both tasks...
October 25, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29149257/eleven-telomere-epigenetic-clock-and-biomarker-composite-quantifications-of-biological-aging-do-they-measure-the-same-thing
#15
Daniel W Belsky, Terrie E Moffitt, Alan A Cohen, David L Corcoran, Morgan E Levine, Joseph A Prinz, Jonathan Schaefer, Karen Sugden, Benjamin Williams, Richie Poulton, Avshalom Caspi
The geroscience hypothesis posits that therapies to slow biological processes of aging can prevent disease and extend healthy years of life. To test such "gero-protective" therapies in humans, outcome measures are needed that can assess extension of disease-free lifespan. This need has spurred development of different methods to quantify biological aging. But different methods have not been systematically compared in the same humans. We implemented seven methods to quantify biological aging using repeated-measures physiological and genomic data in 964 middle-aged humans in the Dunedin Study...
November 15, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/29149067/the-hmgb1-rage-pro-inflammatory-axis-in-the-human-placenta-modulating-effect-of-low-molecular-weight-heparin
#16
Cristian Zenerino, Anna Maria Nuzzo, Domenica Giuffrida, Marilisa Biolcati, Alessandra Zicari, Tullia Todros, Alessandro Rolfo
We evaluated whether physiological and pre-eclamptic (PE) placentae, characterized by exacerbated inflammation, presented alterations in pro-inflammatory High Mobility Group Box 1 (HMGB1) and its Receptor of Advanced Glycation End products (RAGE) expression. Moreover, we investigated, in physiological placental tissue, the ability of Low Molecular Weight Heparin (LMWH) to modify HMGB1 structural conformation thus inhibiting RAGE binding and HMGB1/RAGE axis inflammatory activity. HMGB1, RAGE, IL-6 and TNFα (HMGB1/RAGE targets) mRNA expression were assessed by Real Time PCR...
November 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29148897/oxidative-stress-response-in-sh-sy5y-cells-exposed-to-short-term-1800%C3%A2-mhz-radiofrequency-radiation
#17
Ana Marija Marjanovic Cermak, Ivan Pavicic, Ivancica Trosic
The exact mechanism that could explain the effects of radiofrequency (RF) radiation exposure at non-thermal level is still unknown. Increasing evidence suggests a possible involvement of reactive oxygen species (ROS) and development of oxidative stress. To test the proposed hypothesis, human neuroblastoma cells (SH-SY5Y) were exposed to 1800 MHz short-term RF exposure for 10, 30 and 60 minutes. Electric field strength within Gigahertz Transverse Electromagnetic cell (GTEM) was 30 V m(-1) and specific absorption rate (SAR) was calculated to be 1...
November 17, 2017: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
https://www.readbyqxmd.com/read/29148850/atad2-in-cancer-a-pharmacologically-challenging-but-tractable-target
#18
Muzammal Hussain, Yang Zhou, Yu Song, H M Adnan Hameed, Hao Jiang, Yaoquan Tu, Jiancun Zhang
ATAD2 protein is an emerging oncogene that has strongly been linked to the etiology of multiple advanced human cancers. Therapeutically, despite the fact that genetic suppression/knockdown studies have validated it as a compelling drug target for future therapeutic development, recent druggability assessment data suggest that direct targeting of ATAD2's bromodomain (BRD) may be a very challenging task. ATAD2's BRD has been predicted as a "difficult to drug" or "least druggable" target due to the concern that its binding pocket, and the areas around it, seem to be unfeasible for ligand binding...
November 17, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29148316/recognition-dynamics-of-trinuclear-copper-cluster-and-associated-histidine-residues-through-conserved-or-semi-conserved-water-molecules-in-human-ceruloplasmin-the-involvement-of-aspartic-and-glutamic-acid-gates
#19
Bishnu Prasad Mukhopadhyay
Human Ceruloplasmin belongs to the family of multi-copper oxidases and it is involved in different physiological processes, copper ion transport, iron metabolism, iron homeostasis, and biogenic amine metabolism. MD-simulation studies have indicated the higher hydrophilic susceptibility of the trinuclear copper cluster in native CP compared to its oxygen bound form. The copper (T2/T3) atom Cu3047 of the cluster, which is close to T1 copper center Cu3052 (~13 Å) has a higher affinity for water molecules compared to other copper centers...
November 17, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29148112/big-data-and-data-science-in-healthcare-what-nurses-and-midwives-need-to-know
#20
EDITORIAL
Siobhan O'Connor
The evolution of technology in contemporary society has been accelerating in recent decades, with smaller, more interconnected hardware devices and software applications becoming the norm. As desktop computing paved the way for mobile platforms, which are now transitioning to wearable devices and other sensors, it is inevitable these electronic tools will advance into the realm of nanotechnology and biotechnology in the years to come. As the proliferation of information and communication technology continues it has led to a tsunami of digital data (Bates et al, 2014), which is being collected on many aspects of life...
November 17, 2017: Journal of Clinical Nursing
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