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https://www.readbyqxmd.com/read/29474961/the-presence-of-glutamate-residues-on-the-pas-sequence-of-the-stimuli-sensitive-nano-ferritin-improves-in-vivo-biodistribution-and-mitoxantrone-encapsulation-homogeneity
#1
Elisabetta Falvo, Francesca Malagrinò, Alessandro Arcovito, Francesco Fazi, Gianni Colotti, Elisa Tremante, Patrizio Di Micco, Aldo Braca, Roberta Opri, Alessandro Giuffrè, Giulio Fracasso, Pierpaolo Ceci
A genetically engineered human ferritin heavy chain (HFt)-based construct has been recently shown by our group to efficiently entrap and deliver doxorubicin to cancer cells. This construct, named HFt-MP-PAS, contained a tumor-selective sequence (MP) responsive to proteolytic cleavage by tumor proteases (MMPs), located between each HFt subunit and an outer shielding polypeptide sequence rich in proline (P), serine (S) and alanine (A) residues (PAS). HFt-MP-PAS displayed excellent therapeutic efficacy in xenogenic pancreatic and head and neck cancer models in vivo, leading to a significant increase in overall animal survivals...
February 20, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29474960/anti-tumor-efficacy-of-hyaluronan-based-nanoparticles-for-the-co-delivery-of-drugs-in-lung-cancer
#2
Victor Jeannot, Cony Gauche, Silvia Mazzaferro, Morgane Couvet, Laetitia Vanwonterghem, Maxime Henry, Chloé Didier, Julien Vollaire, Véronique Josserand, Jean-Luc Coll, Christophe Schatz, Sébastien Lecommandoux, Amandine Hurbin
Combinations of therapeutic agents could synergistically enhance the response of lung cancer cells. Co-delivery systems capable of transporting chemotherapeutics with different physicochemical properties and with the simultaneous release of drugs remain elusive. Here, we assess the ability of nanoparticles of 30-nm diameter obtained from the self-assembly of hyaluronan-based copolymer targeting CD44 receptors to encapsulate both gefitinib and vorinostat for effective combinational lung cancer treatment. Drug loading was performed by nanoprecipitation...
February 20, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29474870/improving-revised-international-prognostic-scoring-system-ipss-r-pre-allogeneic-stem-cell-transplant-does-not-translate-into-better-post-transplant-outcomes-for-patients-with-myelodysplastic-syndromes-a-single-center-experience
#3
Musa Alzahrani, Maryse Power, Yasser Abou Mourad, Michael Barnett, Raewyn Broady, Donna Forrest, Alina Gerrie, Donna Hogge, Stephen Nantel, David Sanford, Kevin Song, Heather Sutherland, Cynthia Toze, Thomas Nevill, Sujaatha Narayanan
BACKGROUND: The natural history of patients with myelodysplastic syndromes (MDS) is variable. The revised international prognostic score (IPSS-R) is commonly used in practice to predict outcome in patients with MDS both at diagnosis and pre-transplant. However the effect of change in IPSS-R pre-allogeneic stem cell transplant with chemotherapy or hypomethylating agents on post-transplant outcomes is currently unknown. AIM: We assessed if improvement in IPSS-R prognostic score pre HSCT would result in improvement in clinical outcomes post-transplant...
February 20, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29474075/predicting-the-conformational-variability-of-abl-tyrosine-kinase-using-molecular-dynamics-simulations-and-markov-state-models
#4
Yilin Meng, Cen Gao, David K Clawson, Shane Atwell, Marjanne Russell, Michal Vieth, Benoît Roux
Understanding protein conformational variability remains a challenge in drug discovery. The issue arises in protein kinases, whose multiple conformational states can affect the binding of small-molecule inhibitors. To overcome this challenge, we propose a comprehensive computational framework based on Markov State Models (MSMs). Our framework integrates the information from explicit-solvent molecular dynamics simulations to accurately rank-order the accessible conformational variants of a target protein. We tested the methodology using Abl kinase with a reference and blind-test set...
February 23, 2018: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/29474070/molecular-mechanism-dynamics-and-energetics-of-protein-mediated-dinucleotide-flipping-in-a-mismatched-dna-a-computational-study-of-rad4-dna-complex
#5
Kartheek Pitta, Marimuthu Krishnan
DNA damages alter genetic information and adversely affect gene expression pathways leading to various complex genetic disorders and cancers. DNA repair proteins recognize and rectify DNA damages with high fidelity. A critical molecular event that occurs during most protein-mediated DNA repair processes is the extrusion of orphaned bases at the damaged site facilitated by specific repairing enzymes. The molecular-level understanding of the mechanism, dynamics, and energetics of base extrusion is necessary to elucidate the molecular basis of protein-mediated DNA damage repair...
February 23, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29473284/label-free-monitoring-of-inflammatory-tissue-conditions-using-a-carrageenan-induced-acute-inflammation-rat-model
#6
Seung Ho Lee, Sang Hwa Lee, Jae-Ho Shin, Samjin Choi
Although the confirmation of inflammatory changes within tissues at the onset of various diseases is critical for the early detection of disease and selection of appropriate treatment, most therapies are based on complex and time-consuming diagnostic procedures. Raman spectroscopy has the ability to provide non-invasive, real-time, chemical bonding analysis through the inelastic scattering of photons. In this study, we evaluate the feasibility of Raman spectroscopy as a new, easy, fast, and accurate diagnostic method to support diagnostic decisions...
February 23, 2018: Microscopy Research and Technique
https://www.readbyqxmd.com/read/29473233/highly-augmented-drug-loading-and-stability-of-micellar-nanocomplexes-composed-of-doxorubicin-and-poly-ethylene-glycol-green-tea-catechin-conjugate-for-cancer-therapy
#7
Kun Liang, Joo Eun Chung, Shu Jun Gao, Nunnarpas Yongvongsoontorn, Motoichi Kurisawa
Low drug loading and instability in blood circulation are two key challenges that impede the successful clinical translation of nanomedicine, as they result in only marginal therapeutic efficacy and toxic side effects associated with premature drug leakage, respectively. Herein, highly stable and ultrahigh drug loading micellar nanocomplexes (MNCs) based on the self-assembly of the anticancer drug doxorubicin (DOX) and a poly(ethylene glycol)-epigallocatechin-3-O-gallate (EGCG) conjugate are developed. The formation of these MNCs is facilitated by strong favorable intermolecular interactions between the structurally similar aromatic EGCG and DOX molecules, which impart exceptionally high drug-loading capability of up to 88% and excellent thermodynamic and kinetic stability...
February 23, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29473062/an-ultrasensitive-microchip-electrophoresis-assay-based-on-separation-assisted-double-cycling-signal-amplification-strategy-for-microrna-detection-in-cell-lysate
#8
Kaiji Wei, Jingjin Zhao, Xiaoshu Luo, Senghui Qiu, Fuyun He, Shuting Li, Shulin Zhao
Microchip electrophoresis (MCE) assay is an analysis technique with low consumption and high automation. It is a useful tool in biomedical research and clinical diagnosis. However, the low detection sensitivity limits its application in trace biomarker analysis because of its extremely small sample size. To address the need for high sensitivity in MCE, we have developed an ultrasensitive MCE method based on a separation-assisted double cycling signal amplification strategy for the detection of microRNA (miRNA) in cell lysate...
February 23, 2018: Analyst
https://www.readbyqxmd.com/read/29472356/a-b-cell-receptor-related-gene-signature-predicts-survival-in-mantle-cell-lymphoma-results-from-the-fondazione-italiana-linfomi-mcl-0208-trial
#9
Riccardo Bomben, Simone Ferrero, Tiziana D'Agaro, Michele Dal Bo, Alessandro Re, Andrea Evangelista, Angelo Michele Carella, Alberto Zamò, Umberto Vitolo, Paola Omedè, Chiara Rusconi, Luca Arcaini, Luigi Rigacci, Stefano Luminari, Andrea Piccin, Delong Liu, Adrien Wiestner, Gianluca Gaidano, Sergio Cortelazzo, Marco Ladetto, Valter Gattei
Mantle cell lymphoma patients have variable clinical courses, ranging from indolent cases not requiring immediate treatment to aggressive, rapidly progressing diseases. Thus, diagnostic tools capable to stratify patients according to their risk of relapse and death are warranted. The study included 83 samples from the Fondazione Italiana Linfomi MCL-0208 clinical trial. Through gene expression profiling and quantitative real-time PCR we analyzed 46 peripheral blood and 43 formalin-fixed paraffin-embedded lymph node samples...
February 22, 2018: Haematologica
https://www.readbyqxmd.com/read/29471634/force-fields-for-monovalent-and-divalent-metal-cations-in-tip3p-water-based-on-thermodynamic-and-kinetic-properties
#10
Shavkat Mamatkulov, Nadine Schwierz
Metal cations are essential in many vital processes. In order to capture the role of different cations in all-atom molecular dynamics simulations of biological processes, an accurate parametrization is crucial. Here, we develop force field parameters for the metal cations Li+ , Na+ , K+ , Cs+ , Mg2+ , Ca2+ , Sr2+ , and Ba2+ in combination with the TIP3P water model that is frequently used in biomolecular simulations. In progressing toward improved force fields, the approach presented here is an extension of previous efforts and allows us to simultaneously reproduce thermodynamic and kinetic properties of aqueous solutions...
February 21, 2018: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29471025/releasing-iron-from-ferritin-protein-nanocage-by-reductive-method-the-role-of-electron-transfer-mediator
#11
Prashanth Kumar Koochana, Abhinav Mohanty, Suman Das, Biswamaitree Subhadarshanee, Suresh Satpati, Anshuman Dixit, Surendra Chandra Sabat, Rabindra K Behera
BACKGROUND: Ferritin detoxifies excess of free Fe(II) and concentrates it in the form of ferrihydrite (Fe2 O3 ·xH2 O) mineral. When in need, ferritin iron is released for cellular metabolic activities. However, the low solubility of Fe(III) at neutral pH, its encapsulation by stable protein nanocage and presence of dissolved O2 limits in vitro ferritin iron release. METHODS: Physiological reducing agent, NADH (E1/2  = -330 mV) was inefficient in releasing ferritin iron (E1/2  = +183 mV), when used alone...
February 19, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29470528/linear-relationship-between-peak-and-season-long-abundances-in-insects
#12
Ksenia S Onufrieva, Alexey V Onufriev
An accurate quantitative relationship between key characteristics of an insect population, such as season-long and peak abundances, can be very useful in pest management programs. To the best of our knowledge, no such relationship has yet been established. Here we establish a predictive linear relationship between insect catch Mpw during the week of peak abundance, the length of seasonal flight period, F (number of weeks) and season-long cumulative catch (abundance) A = 0.41MpwF. The derivation of the equation is based on several general assumptions and does not involve fitting to experimental data, which implies generality of the result...
2018: PloS One
https://www.readbyqxmd.com/read/29469077/carboplatin-based-concurrent-chemoradiation-therapy-in-locally-advanced-head-and-neck-cancer-patients-who-are-unfit-for-cisplatin-therapy
#13
V Noronha, V Sharma, A Joshi, V M Patil, S G Laskar, K Prabhash
BACKGROUND: Cisplatin-based chemoradiation (CTRT) is the standard of care in locally advanced head and neck cancers. Limited treatment options are available in patients unfit for cisplatin. AIMS: This audit was carried out to study the toxicities, tolerance, and outcomes of carboplatin-based CTRT in patients who are not eligible for cisplatin. MATERIALS AND METHODS: A total of 63 locally advanced head and neck cancer patients treated between January 2011 and October 2015 were administered carboplatin-based CTRT...
April 2017: Indian Journal of Cancer
https://www.readbyqxmd.com/read/29468602/time-series-disturbance-detection-for-hypothesis-free-signal-detection-in-longitudinal-observational-databases
#14
Ed Whalen, Manfred Hauben, Andrew Bate
INTRODUCTION: Signal detection remains a cornerstone activity of pharmacovigilance. Routine quantitative signal detection primarily focuses on screening of spontaneous reports. In striving to enhance quantitative signal detection capability further, other data streams are being considered for their potential contribution as sources of emerging signals, one of which is longitudinal observational databases, including electronic medical record (EMR) and transactional insurance claims databases...
February 21, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/29468564/early-presymptomatic-changes-in-the-proteome-of-mitochondria-associated-membrane-in-the-app-ps1-mouse-model-of-alzheimer-s-disease
#15
Katalin Völgyi, Kata Badics, Fernando J Sialana, Péter Gulyássy, Edina Brigitta Udvari, Viktor Kis, László Drahos, Gert Lubec, Katalin Adrienna Kékesi, Gábor Juhász
Intracellular β-amyloid (Aβ) accumulation is an early event in Alzheimer's disease (AD) progression. Recently, it has been uncovered that presenilins (PSs), the key components of the amyloid precursor protein (APP) processing and the β-amyloid producing γ-secretase complex, are highly enriched in a special sub-compartment of the endoplasmic reticulum (ER) functionally connected to mitochondria, called mitochondria-associated ER membrane (MAM). A current hypothesis of pathogenesis of Alzheimer's diseases (AD) suggests that MAM is involved in the initial phase of AD...
February 22, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29468446/cost-effectiveness-of-the-long-term-use-of-temozolomide-for-treating-newly-diagnosed-glioblastoma-in-germany
#16
Albrecht Waschke, Habibollah Arefian, Jan Walter, Michael Hartmann, Jens Maschmann, Rolf Kalff
Concomitant radiochemotherapy followed by six cycles of temozolomide (= short term) is considered as standard therapy for adults with newly diagnosed glioblastoma. In contrast, open-end administration of temozolomide until progression (= long-term) is proposed by some authors as a viable alternative. We aimed to determine the cost-effectiveness of long-term temozolomide therapy for patients newly diagnosed with glioblastoma compared to standard therapy. A Markov model was constructed to compare medical costs and clinical outcomes for both therapy types over a time horizon of 60 months...
February 21, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29467823/in-vitro-and-in-vivo-characterization-of-three-cellvibrio-japonicus-glycoside-hydrolase-family-5-members-reveals-potent-xyloglucan-backbone-cleaving-functions
#17
Mohamed A Attia, Cassandra E Nelson, Wendy A Offen, Namrata Jain, Gideon J Davies, Jeffrey G Gardner, Harry Brumer
Background: Xyloglucan (XyG) is a ubiquitous and fundamental polysaccharide of plant cell walls. Due to its structural complexity, XyG requires a combination of backbone-cleaving and sidechain-debranching enzymes for complete deconstruction into its component monosaccharides. The soil saprophyte Cellvibrio japonicus has emerged as a genetically tractable model system to study biomass saccharification, in part due to its innate capacity to utilize a wide range of plant polysaccharides for growth...
2018: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29467438/lifetime-of-racetrack-skyrmions
#18
Pavel F Bessarab, Gideon P Müller, Igor S Lobanov, Filipp N Rybakov, Nikolai S Kiselev, Hannes Jónsson, Valery M Uzdin, Stefan Blügel, Lars Bergqvist, Anna Delin
The skyrmion racetrack is a promising concept for future information technology. There, binary bits are carried by nanoscale spin swirls-skyrmions-driven along magnetic strips. Stability of the skyrmions is a critical issue for realising this technology. Here we demonstrate that the racetrack skyrmion lifetime can be calculated from first principles as a function of temperature, magnetic field and track width. Our method combines harmonic transition state theory extended to include Goldstone modes, with an atomistic spin Hamiltonian parametrized from density functional theory calculations...
February 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29466707/iron-transport-kinetics-through-blood-brain-barrier-endothelial-cells
#19
Aminul Islam Khan, Jin Liu, Prashanta Dutta
BACKGROUND: Transferrin and its receptors play an important role during the uptake and transcytosis of iron through blood-brain barrier (BBB) endothelial cells (ECs) to maintain iron homeostasis in BBB endothelium and brain. Any disruptions in the cell environment may change the distribution of transferrin receptors on the cell surface, which eventually alter the homeostasis and initiate neurodegenerative disorders. In this paper, we developed a comprehensive mathematical model that considers the necessary kinetics for holo-transferrin internalization and acidification, apo-transferrin recycling, and exocytosis of free iron and transferrin-bound iron through basolateral side of BBB ECs...
February 18, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29466505/molecular-detection-of-anaplasmataceae-agents-in-dasyprocta-azarae-in-northeastern-brazil
#20
Maria do Socorro Costa de Oliveira Braga, José Gomes Pereira, Simone de Jesus Fernandes, Ingrid Carolinne Lopes Marques, Renata Passos de Jesus, Gleycianny Santos Ferreira, Daniele Rosa Xavier, Jyan Lucas Benevenute, Rosangela Zacarias Machado, Marcos Rogério André
Recently, the importance of wild-living rodents for maintenance of pathogens of the family Anaplasmataceae in the environment was investigated. These mammals play a role as reservoirs for these pathogens and act as hosts for the immature stages of tick vectors. The aim of the present study was to investigate the prevalence of Ehrlichia sp. and Anaplasma sp. in 24 specimens of Azara's agouti (Dasyprocta azarae) that had been trapped in the Itapiracó Environmental Reserve, in São Luís, Maranhão, northeastern Brazil, using molecular methods...
February 19, 2018: Revista Brasileira de Parasitologia Veterinária, Brazilian Journal of Veterinary Parasitology
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