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https://www.readbyqxmd.com/read/29458212/programmed-drug-delivery-system-based-on-optimized-size-decrease-and-hydrophilicity-hydrophobicity-transformation-for-enhanced-hepatocellular-carcinoma-therapy-of-doxorubicin
#1
Yuanyuan Liu, Lian Li, Lijia Li, Zhou Zhou, Fengling Wang, Xiaofeng Xiong, Rui Zhou, Yuan Huang
Requirements on drug delivery systems to surmount a complex series of pathophysiological barriers bear "cascading contradictions", especially size and hydrophilicity/hydrophobicity contradiction. Herein, a programmed drug delivery system (GNPs-Dox-Lac) based on optimized "size decrease and hydrophilicity/hydrophobicity transformation" was developed by combination the gelatin nanoparticle (GNPs) and prodrug Doxorubicin-Lactose (Dox-Lac). The results showed that GNPs-Dox-Lac (133.3 nm) were kinetically stable in blood circulation and inclined to accumulate at the tumor site...
February 16, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29458203/precision-pharmacology-for-alzheimer-s-disease
#2
REVIEW
Harald Hampel, Andrea Vergallo, Lisi Flores Aguilar, Norbert Benda, Karl Broich, A Claudio Cuello, Jeffrey Cummings, Bruno Dubois, Howard J Federoff, Massimo Fiandaca, Remy Genthon, Marion Haberkamp, Eric Karran, Mark Mapstone, George Perry, Lon S Schneider, Lindsay A Welikovitch, Janet Woodcock, Filippo Baldacci, Simone Lista
The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses...
February 16, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29458177/colorimetric-detection-of-microrna-based-on-dnazyme-and-nuclease-assisted-catalytic-hairpin-assembly-signal-amplification
#3
Hongmei Zhang, Kuiyu Wang, Shengjun Bu, Zhongyi Li, Chuanjing Ju, Jiayu Wan
Accurate and quantitative analysis of microRNA (miRNA) expression is critical for the diagnostics and theranostics of a disease. Herein, a proof-of-concept of a colorimetric horseradish peroxidase-mimicking DNAzyme (HRP-DNAzyme) biosensor for miRNA assay based on nuclease-assisted catalytic hairpin assembly (CHA) signal amplification was demonstrated. Duplex-specific nuclease (DSN) was employed to cleave the single-stranded DNA (ssDNA) chimeric probe (CP) on the magnetic bead (MB) surface via hybridization of the CP and target miRNA...
February 16, 2018: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/29458168/apoptosis-of-enterocytes-and-nitration-of-junctional-complex-proteins-promote-alcohol-induced-gut-leakiness-and-liver-injury
#4
Young-Eun Cho, Li-Rong Yu, Mohamed A Abdelmegeed, Seong-Ho Yoo, Byoung-Joon Song
BACKGROUND & AIMS: Binge alcohol causes gut leakiness, contributing to increased endotoxemia and inflammatory liver injury, although the molecular mechanisms are still elusive. This study was aimed at investigating the roles of apoptosis of enterocytes and nitration followed by degradation of intestinal tight junction (TJ) and adherent junction (AJ) proteins in binge alcohol-induced gut leakiness. METHODS: The levels of intestinal (ileum) junctional complex proteins, oxidative stress markers and apoptosis-related proteins in rodents, T84 colonic cells and autopsied human ileums were determined by immunoblot, immunoprecipitation, immunofluorescence, and mass-spectral analyses...
February 16, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29458152/controversies-in-endoscopic-eradication-therapy-for-barrett-s-esophagus
#5
Srinadh Komanduri, V Raman Muthusamy, Sachin Wani
Advances in Endoscopic Eradication Therapy for Barrett's Esophagus associated neoplasia have resulted in a significant paradigm shift in diagnosis and management of this complex disease. A robust body of literature critically evaluating outcomes of resection and ablative strategies has allowed gastroenterologists to make quality, evidence based decisions for their patients. Despite this progress, there are still many unanswered questions and challenges that remain. Ultimately, identification of a cost-effective screening modality, biomarkers for risk stratification, and strides to eliminate post surveillance endoscopy after EET are essential to reach our long term goal for eradication of esophageal adenocarcinoma...
February 16, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29458144/disruption-of-peroxisome-function-leads-to-metabolic-stress-mtor-inhibition-and-lethality-in-liver-cancer-cells
#6
Mengjiao Cai, Xiao Sun, Wenchao Wang, Zhusheng Lian, Ping Wu, Suxia Han, Huan Chen, Pumin Zhang
Peroxisome houses a large number of enzymes involved in lipid and phytochemical oxidation as well as synthesis of bile acid and other specialized lipids. Peroxisome resident enzymes are imported into the organelle via a conserved cargo transport system composed of many peroxins, protein factors essential for the biogenesis of peroxisome. Among the peroxins, PEX5 plays a transporter role, and PEX2, 10, and 12 are thought to form a complex that functions as an E3 ubiquitin ligase to help recycle PEX5 in an ubiquitin modification-dependent process...
February 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29458141/long-non-coding-rnas-within-the-tumour-microenvironment-and-their-role-in-tumour-stroma-cross-talk
#7
Filippo Del Vecchio, Gui Han Lee, Joamir Hawezi, Rahul Bhome, Sian Pugh, Emre Sayan, Gareth Thomas, Graham Packham, John Primrose, Martin Pichler, Alexander Mirnezami, George Calin, Marc Bullock
Long non-coding RNAs (lncRNAs) are a diverse class of RNA transcripts which have limited protein coding potential. They perform a variety of cellular functions in health, but have also been implicated during malignant transformation. A further theme in recent years is the critical role of the tumour microenvironment and the dynamic interactions between cancer and stromal cells in promoting invasion and disease progression. Whereas the contribution of deregulated lncRNAs within cancer cells has received considerable attention, their significance within the tumour microenvironment is less well understood...
February 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29458137/bisphenol-a-alters-oocyte-maturation-by-prematurely-closing-gap-junctions-in-the-cumulus-cell-oocyte-complex
#8
Deyanira Guadalupe Acuña-Hernández, Laura Arreola-Mendoza, Ramsés Santacruz-Márquez, Sihomara Patricia García-Zepeda, Lyda Yuliana Parra-Forero, Jesús Alberto Olivares-Reyes, Isabel Hernández-Ochoa
In ovarian follicles, cumulus cells communicate with the oocyte through gap junction intercellular communication (GJIC), to nurture the oocyte and control its meiosis arrest and division. Bisphenol A (BPA) is a monomer found in polycarbonate-made containers that can induce functional alterations, including impaired oocyte meiotic division and reduced molecule transfer in GJIC. However, how BPA alters oocyte meiotic division is unclear. We investigated whether BPA effects on oocyte meiotic division were correlated with reduced transfer in GJIC...
February 16, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29458128/aggregation-prone-regions-in-hypk-help-it-to-form-sequestration-complex-for-toxic-protein-aggregates
#9
Debasish Kumar Ghosh, Ajit Roy, Akash Ranjan
Protein aggregates result from altered structural conformations and they can perturb cellular homeostasis. Prevention mechanisms, which function against protein aggregation by modulatory processes, are diverse and redundant. In this study, we have characterized Huntingtin interacting protein K (HYPK) as a global aggregation-regulatory protein. We report the mechanistic details of how HYPK's aggregation-prone regions allow it to sense and prevent other toxic protein's aggregation by forming unique annular-shaped sequestration complexes...
February 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29458124/tryptophan-mediated-dimerization-of-the-tssl-transmembrane-anchor-is-required-for-type-vi-secretion-system-activity
#10
Abdelrahim Zoued, Jean-Pierre Duneau, Eric Durand, Alexandre P España, Laure Journet, Françoise Guerlesquin, Eric Cascales
The Type VI secretion system (T6SS) is a multiprotein complex used by bacteria to deliver effectors into target cells. The T6SS comprises a bacteriophage-like contractile tail structure anchored to the cell envelope by a membrane complex constituted of the TssJ outer membrane lipoprotein and the TssL and TssM inner membrane proteins. TssJ establishes contact with the periplasmic domain of TssM whereas the transmembrane segments of TssM and its cytoplasmic domain interact with TssL. TssL protrudes in the cytoplasm but is anchored by a C-terminal transmembrane helix (TMH)...
February 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29458114/severity-dependent-influence-of-isocapnic-hypoxia-on-reaction-time-is-independent-of-neurovascular-coupling
#11
Hannah G Caldwell, Geoff B Coombs, Michael M Tymko, Daniela Nowak-Flück, Philip N Ainslie
With exposure to acute normobaric hypoxia, global cerebral oxygen delivery is maintained via increases in cerebral blood flow (CBF); therefore, regional and localized changes in oxygen tension may explain neurocognitive impairment. Neurovascular coupling (NVC) is the close temporal and regional relationship of CBF to changes in neural activity and may aid in explaining the localized CBF response with cognitive activation. High-altitude related cognitive impairment is likely affected by hypocapnic cerebral vasoconstriction that may influence regional CBF regulation independent of hypoxia...
February 16, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29458112/compatible-osmolytes-modulate-mitochondrial-function-in-a-marine-osmoconformer-crassostrea-gigas-thunberg-1793
#12
Eugene P Sokolov, Inna M Sokolova
Salinity is an important environmental factor affecting physiology of marine organisms. Osmoconformers such as marine mollusks maintain metabolic function despite changes of the osmolarity and composition of the cytosol during salinity shifts. Currently, metabolic responses to the salinity-induced changes of the intracellular milieu are not well understood. We studied the effects of osmolarity (450 vs. 900 mOsm) and compatible osmolytes (70-590 mM of taurine or betaine) on isolated gill mitochondria of a marine osmoconformer, the Pacific oyster Crassostrea gigas...
February 16, 2018: Mitochondrion
https://www.readbyqxmd.com/read/29458108/the-relaxin-receptor-as-a-therapeutic-target-perspectives-from-evolution-and-drug-targeting
#13
REVIEW
Ross A D Bathgate, Martina Kocan, Daniel J Scott, M Akhter Hossain, Sara V Good, Sergey Yegorov, Jan Bogerd, Paul Gooley
The peptide relaxin was first identified as an important circulating hormone during pregnancy over 90 years ago. Research over many years defined the numerous biological roles that relaxin plays throughout pregnancy in many mammalian species. These important biological actions have led to the testing of relaxin as a therapeutic agent for a number of indications. The discovery of the relaxin receptor, RXFP1, in 2002 facilitated the better understanding of the cellular targets of relaxin, its mechanism of action and enabled the development of relaxin mimetics and screening for small molecule agonists...
February 16, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29458097/topographical-memory-analyzed-in-mice-using-the-hamlet-test-a-novel-complex-maze
#14
Lucie Crouzier, Damien Gilabert, Mireille Rossel, Françoise Trousse, Tangui Maurice
The Hamlet test is an innovative device providing a complex environment for testing topographic memory in mice. Animals were trained in groups for weeks in a small village with a central agora, streets expanding from it towards five functionalized houses, where they can drink, eat, hide, run, interact with a stranger mouse. Memory was tested by depriving mice from water or food and analyzing their ability to locate the Drink/Eat house. Exploration and memory were analysed in different strains, gender, and after different training periods and delays...
February 16, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29458092/ramifications-of-the-children-s-surgery-verification-program-for-patients-and-hospitals
#15
Katherine J Baxter, Bonnie F Gale, Curtis D Travers, Kurt F Heiss, Mehul V Raval
BACKGROUND: The American College of Surgeons in 2015 instituted the Children's Surgery Verification (CSV) program delineating requirements for hospitals providing pediatric surgical care. Our purpose was to examine possible effects of the CSV program by evaluating neonates undergoing high-risk operations. STUDY DESIGN: Using the Kid's Inpatient Database 2009, we identified infants undergoing surgery for five high risk neonatal conditions. We considered all children's hospitals and children's units Level I centers and considered all others Level II/III...
February 16, 2018: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/29458089/structural-and-biophysical-insight-into-dual-site-binding-of-the-protoberberine-alkaloid-palmatine-to-parallel-g-quadruplex-dna-using-nmr-fluorescence-and-circular-dichroism-spectroscopy
#16
Kumar Padmapriya, Ritu Barthwal
Plant derived small molecules, which interact with and stabilize G-quadruplex DNA, act as inhibitors of telomere elongation and oncogene expression in humans. The inhibition of telomerase enzyme has immense potential since it is over expressed in most cancer cells. Interaction of palmatine, an antitumor alkaloid, to parallel G-quadruplex DNA, [d(TTGGGGT)]4 and [d(TTAGGGT)]4 , has been investigated using Nuclear Magnetic Resonance (NMR), fluorescence and Circular Dichroism (CD) spectroscopy. Titrations were monitored by1 H and31 P NMR spectra and solution structure of palmatine-[d(TTGGGGT)]4 complex was obtained by restrained Molecular Dynamics (rMD) simulations using distance restraints from 2D NOESY spectra...
February 16, 2018: Biochimie
https://www.readbyqxmd.com/read/29458077/reciprocal-regulation-of-the-cadherin-11-stat3-axis-by-caveolin-1-in-mouse-fibroblasts-and-lung-carcinoma-cells
#17
M Geletu, R Mohan, R Arulanandam, A Berger-Becvar, I R Nabi, P T Gunning, L Raptis
Caveolin-1 (Cav1) is an integral plasma membrane protein and a complex regulator of signal transduction. The Signal Transducer and Activator of Transcription-3 (Stat3) is activated by a number of receptor and non-receptor tyrosine kinases and is positively implicated in cancer. Despite extensive efforts, the relationship between Cav1 and Stat3 has been a matter of controversy. We previously demonstrated that engagement of E- or N-cadherin or cadherin-11 cell to cell adhesion molecules, as occurs with confluence of cultured cells, triggers a dramatic increase in the levels of tyr705 phosphorylated ie activated Stat3, by a mechanism requiring the cRac1 small GTPase...
February 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29458057/roles-of-the-insulin-signaling-pathway-in-insect-development-and-organ-growth
#18
Xianyu Lin, Guy Smagghe
Organismal development is a complex process as it requires coordination of many aspects to grow into fit individuals, such as the control of body size and organ growth. Therefore, the mechanisms of precise control of growth are essential for ensuring the growth of organisms at a correct body size and proper organ proportions during development. The control of the growth rate and the duration of growth (or the cessation of growth) are required in size control. The insulin signaling pathway and the elements involved are essential in the control of growth...
February 16, 2018: Peptides
https://www.readbyqxmd.com/read/29458054/comparative-investigation-of-binding-interactions-with-three-steroidal-derivatives-of-d-gggt-4-g-quadruplex-aptamer
#19
Shan Huang, Yu Liang, Jianguo Cui, Jiangning Xie, Yi Liu, Baoqing Hu, Qi Xiao
Steroidal derivatives have attracted tremendous attentions in biological and biomedical areas, due to their variety biological activities. The investigation of structural influences helps in understanding their biological activities. The interactions of steroidal derivatives with DNA may play important roles in biological activities, however only a few investigations were reported on this issue. Herein, the structural influences of three steroidal derivatives were investigated based on their binding interactions with d(GGGT)4 G-quadruplex aptamer by spectroscopic approaches, nuclear magnetic resonance (NMR), electrochemical methods, and molecular modeling techniques...
February 16, 2018: Steroids
https://www.readbyqxmd.com/read/29458042/pretreatment-with-cholesterol-loaded-cyclodextrins-prevents-loss-of-motility-associated-proteins-during-cryopreservation-of-addra-gazelle-nanger-dama-ruficollis-spermatozoa
#20
Jessye Wojtusik, Yan Wang, Budhan S Pukazhenthi
Sperm cryopreservation is challenging, often resulting in irreversible damage to spermatozoa, as indicated by decreased motility, viability, and/or acrosomal integrity. Developing cryopreservation protocols for gametes of endangered species compounds the complexity of technique optimization; samples are difficult to obtain and numbers are limited. Cryopreservation of sperm collected from the critically endangered addra gazelle (Nanger dama ruficollis), a member of the Bovidae family, resulted in significant loss of motility, which was prevented by pretreatment with cholesterol-loaded cyclodextrin (CLC)...
February 16, 2018: Cryobiology
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