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https://www.readbyqxmd.com/read/29353230/a-model-of-dormant-emergent-metastatic-breast-cancer-progression-enabling-exploration-of-biomarker-signatures
#1
Amanda M Clark, Manu Kumar, Sarah Wheeler, Carissa Young, Raman Venkataramanan, Donna Stolz, Linda Griffith, Douglas A Lauffenburger, Alan Wells
Breast cancer mortality predominantly results from dormant micrometastases that emerge as fatal outgrowths years after initial diagnosis. In order to gain insights concerning factors associated with emergence of liver metastases, we recreated spontaneous dormancy in an all-human ex vivo hepatic microphysiological system (MPS). Seeding this MPS with small numbers (<0.05% by cell count) of the aggressive MDA-MB-231 breast cancer cell line, two populations formed: actively proliferating ('growing'; EdU+), and spontaneously quiescent ('dormant'; EdU-)...
January 20, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29353158/quantification-of-light-induced-minisog-superoxide-production-using-the-selective-marker-2-hydroxyethidium
#2
Miriam E Barnett, Timothy M Baran, Thomas H Foster, Andrew P Wojtovich
Genetically-encoded photosensitizers produce reactive oxygen species (ROS) in response to light. Transgenic expression of fusion proteins can target the photosensitizers to specific cell regions and permit the spatial and temporal control of ROS production. These ROS-generating proteins (RGPs) are widely used for cell ablation, mutagenesis and chromophore-assisted light inactivation of target proteins. However, the species produced by RGPs are unclear due to indirect measures with confounding interpretations...
January 17, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29353012/fabrication-of-poly-ethylene-glycol-coated-mesoporous-nanocomposite-zno-fe2o3-for-methotrexate-delivery-an-integrated-nanoplatform-for-dual-mode-cancer-therapy
#3
Azam S Alavi, Azadeh Meshkini
Although chemotherapy is an effective strategy for treatment of tumor cells, the non-specific distribution of chemotherapy drugs and their poor aqueous solubility result in impaired treatment and cause serious side effects in patients. In this study, mesoporous ZnO@Fe2O3 nanocomposite was fabricated and used as a platform for drug delivery. ZnO@Fe2O3 nanocomposite showed a high capacity for the adsorption of chemotherapy drug, methotrexate (MTX). Drug-loaded nanoparticle was coated with poly(ethylene glycol) (PEG), leading to the enhanced colloidal stability and good cytocompatibility...
January 15, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29352273/binder-free-sheet-type-all-solid-state-batteries-with-enhanced-rate-capabilities-and-high-energy-densities
#4
Mari Yamamoto, Yoshihiro Terauchi, Atsushi Sakuda, Masanari Takahashi
All-solid-state batteries using inorganic solid electrolytes are considered promising energy storage systems because of their safety and long life. Stackable and compact sheet-type all-solid-state batteries are urgently needed for industrial applications such as smart grids and electric vehicles. A binder is usually indispensable to the construction of sheet-type batteries; however, it can decrease the power and cycle performance of the battery. Here we report the first fabrication of a binder-free sheet-type battery...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29351476/human-endoc-%C3%AE-h1-%C3%AE-cells-form-pseudoislets-with-improved-glucose-sensitivity-and-enhanced-glp-1-signaling-in-the-presence-of-islet-derived-endothelial-cells
#5
Michael G Spelios, Lauren A Afinowicz, Regine C Tipon, Eitan M Akirav
Three-dimensional (3D) pseudoislets (PIs) can be used for the study of insulin-producing β-cells in free-floating islet-like structures similar to that of primary islets. Previously, we demonstrated the ability of islet-derived endothelial cells (iECs) to induce PIs using murine insulinomas, where PI formation enhanced insulin production and glucose responsiveness. In this report, we examined the ability of iECs to spontaneously induce the formation of free-floating 3D PIs using the EndoC-βH1 human β-cell line murine MS1 iEC line...
January 16, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29350922/computing-curvature-sensitivity-of-biomolecules-in-membranes-by-simulated-buckling
#6
Federico Elias-Wolff, Martin Lindén, Alexander P Lyubartsev, Erik G Brandt
Membrane curvature sensing, where the binding free energies of membrane-associated molecules depend on the local membrane curvature, is a key factor to modulate and maintain the shape and organization of cell membranes. However, the microscopic mechanisms are not well understood, partly due to absence of efficient simulation methods. Here, we describe a method to compute the curvature dependence of the binding free energy of a membrane-associated probe molecule that interacts with a buckled membrane, which has been created by lateral compression of a flat bilayer patch...
January 19, 2018: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/29350186/mri-tracing-non-invasive-tio2-based-nanoparticles-motivated-by-ultrasound-for-multi-mechanism-therapy-of-prostatic-cancer
#7
Pu Yuan, Dongkui Song
To reduce the side effects of chemotherapy and reach effective and safe therapy of prostate cancer, herein, a simple but multifunctional system TiO2:Gd@DOX/FA motivated by ultrasound was developed for MRI guided multi-mechanism therapy of prostate cancer. TiO2 nanoparticles served as a sonosensitizer as well as a nanocarrier with pH-responsive release of DOX. Doping of Gd could not only endow TiO2 the ability of magnetic resonance imaging (MRI), but also further improve sonodynamic ability of TiO2. The characterization revealed the as-prepared TiO2:Gd@DOX/FA showed sensitive pH-responsive drug release, high ROS production, T1-MRI contrast performance and excellent biocompatibility...
January 19, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29349663/ibandronate-metal-complexes-solution-behavior-and-antiparasitic-activity
#8
Bruno Demoro, Santiago Rostán, Mauricio Moncada, Zhu-Hong Li, Roberto Docampo, Claudio Olea Azar, Juan Diego Maya, Julia Torres, Dinorah Gambino, Lucía Otero
To face the high costs of developing new drugs, researchers in both industry and academy are looking for ways to repurpose old drugs for new uses. In this sense, bisphosphonates that are clinically used for bone diseases have been studied as agents against Trypanosoma cruzi, causative parasite of Chagas disease. In this work, the development of first row transition metal complexes (M = Co2+, Mn2+, Ni2+) with the bisphosphonate ibandronate (iba, H4iba representing the neutral form) is presented. The in-solution behavior of the systems containing iba and the selected 3d metal ions was studied by potentiometry...
January 18, 2018: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/29348856/prognostic-value-of-diametrically-polarized-tumor-associated-macrophages-in-multiple-myeloma
#9
Xinyi Chen, Jin Chen, Wenyan Zhang, Ruixue Sun, Ting Liu, Yuhuan Zheng, Yu Wu
Tumor-associated macrophages (TAMs) are correlated with the prognosis of different types of solid tumors and lymphoma, according to many clinical studies. In vitro experiments have demonstrated the roles of these cells in myeloma cell survival, angiogenesis, immunomodulation, drug resistance, and the interaction between malignant myeloma cells and the microenvironment. Here, we investigated the prognostic significance of TAMs in patients with multiple myeloma (MM). We evaluated the polarized functional status of bone marrow infiltrated by TAMs by immunohistochemical staining of CD68, iNOS, and CD163 in 240 patients with MM from January 2009 to December 2014...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348522/in-vitro-and-in-vivo-antimicrobial-activity-of-ts2037-a-novel-aminoglycoside-antibiotic
#10
Yoko Hirai, Kazunori Maebashi, Hideki Fushimi, Yukiko Hiraiwa, Shoichi Murakami, Takayuki Usui, Yoshihisa Akiyama, Nobuto Minowa, Daishiro Ikeda
To overcome serious methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa infections, we synthesized TS2037, 5,4″-diepi-arbekacin, a novel aminoglycoside antibiotic, and evaluated its biological properties. TS2037 showed broad-range, as well as robust antibacterial activities against Gram-positive and Gram-negative bacteria. The MIC50 and MIC90 of TS2037 against clinical isolates of MRSA (n = 54) were both 0.25 µg/mL, and no resistant strain was observed. The MIC50 and MIC90 of TS2037 against clinical isolates of P...
January 18, 2018: Journal of Antibiotics
https://www.readbyqxmd.com/read/29348491/order-enables-efficient-electron-hole-separation-at-an-organic-heterojunction-with-a-small-energy-loss
#11
S Matthew Menke, Alexandre Cheminal, Patrick Conaghan, Niva A Ran, Neil C Greehnam, Guillermo C Bazan, Thuc-Quyen Nguyen, Akshay Rao, Richard H Friend
Donor-acceptor organic solar cells often show low open-circuit voltages (V OC) relative to their optical energy gap (E g) that limit power conversion efficiencies to ~12%. This energy loss is partly attributed to the offset between E g and that of intermolecular charge transfer (CT) states at the donor-acceptor interface. Here we study charge generation occurring in PIPCP:PC61BM, a system with a very low driving energy for initial charge separation (E g-E CT ~ 50 meV) and a high internal quantum efficiency (η IQE ~ 80%)...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29347993/updated-efficacy-of-avelumab-in-patients-with-previously-treated-metastatic-merkel-cell-carcinoma-after-%C3%A2-1%C3%A2-year-of-follow-up-javelin-merkel-200-a-phase-2-clinical-trial
#12
Howard L Kaufman, Jeffery S Russell, Omid Hamid, Shailender Bhatia, Patrick Terheyden, Sandra P D'Angelo, Kent C Shih, Céleste Lebbé, Michele Milella, Isaac Brownell, Karl D Lewis, Jochen H Lorch, Anja von Heydebreck, Meliessa Hennessy, Paul Nghiem
BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with poor survival outcomes in patients with distant metastatic disease (mMCC). In an initial analysis from JAVELIN Merkel 200, a phase 2, prospective, open-label, single-arm trial in mMCC, avelumab-a human anti-programmed death-ligand 1 (PD-L1) monoclonal antibody-showed promising efficacy and a safety profile that was generally manageable and tolerable. Here, we report the efficacy of avelumab after ≥1 year of follow-up in patients with distant mMCC that had progressed following prior chemotherapy for metastatic disease...
January 19, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29347247/multivalent-ligand-receptor-mediated-interaction-of-small-filled-vesicles-with-a-cellular-membrane
#13
Vladimir P Zhdanov
The ligand-receptor-mediated contacts of small sub-100-nm-sized lipid vesicles (or nanoparticles) with the cellular membrane are of interest in the contexts of cell-to-cell communication, endocytosis of membrane-coated virions, and drug (RNA) delivery. In all these cases, the interior of vesicles is filled by biologically relevant content. Despite the diversity of such systems, the corresponding ligand-receptor interaction possesses universal features. One of them is that the vesicle-membrane contacts can be accompanied by the redistribution of ligands and receptors between the contact and contact-free regions...
July 2017: Physical Review. E
https://www.readbyqxmd.com/read/29345979/machine-learning-enables-live-label-free-phenotypic-screening-in-three-dimensions
#14
Eoghan O'Duibhir, Jasmin Paris, Hannah Lawson, Catarina Sepulveda, Dahlia Doughty Shenton, Neil O Carragher, Kamil R Kranc
There is a large amount of information in brightfield images that was previously inaccessible by using traditional microscopy techniques. This information can now be exploited by using machine-learning approaches for both image segmentation and the classification of objects. We have combined these approaches with a label-free assay for growth and differentiation of leukemic colonies, to generate a novel platform for phenotypic drug discovery. Initially, a supervised machine-learning algorithm was used to identify in-focus colonies growing in a three-dimensional (3D) methylcellulose gel...
January 2018: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/29345455/3d-printing-of-bisphenol-a-free-polycarbonates
#15
Wei Zhu, Sang-Hyun Pyo, Pengrui Wang, Shangting You, Claire Yu, Jeffrey Alido, Justin Liu, Yew Leong, Shaochen Chen
Polycarbonates are widely used in food packages, drink bottles, and various healthcare products such as dental sealants and tooth coatings. However, bisphenol A (BPA) and phosgene used in the production of commercial polycarbonates poses major concerns to public health safety. Here, we report a green pathway to prepare BPA-free polycarbonates (BFPs) by thermal ring opening polymerization and photopolymerization. Polycarbonates prepared from two cyclic carbonates in different mole ratios demonstrated tunable mechanical stiffness, excellent thermal stability, and high optical transparency...
January 18, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29344877/a-bioluminescent-test-system-reveals-valuable-antioxidant-properties-of-lactobacillus-strains-from-human-microbiota
#16
Maria Marsova, Serikbay Abilev, Elena Poluektova, Valeriy Danilenko
Oxidative stress cause serious damages in human organism resulting in multiple diseases. Antioxidant therapy includes diet, the use of chemical agents or commensal bacteria such as lactobacilli. This study aims to evaluate the antioxidant (AO) activity of cell-free culture supernatants of lactobacilli, isolated from different parts of the human body. A test system based on Escherichia coli MG1655 strains carrying plasmids encoding luminescent biosensors pSoxS-lux and pKatG-lux inducible by superoxide anion and hydrogen peroxide, respectively, was used to analyze cell-free culture supernatants of lactobacilli...
January 17, 2018: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/29344809/regeneration-of-functional-alveoli-by-adult-human-sox9-airway-basal-cell-transplantation
#17
Qiwang Ma, Yu Ma, Xiaotian Dai, Tao Ren, Yingjie Fu, Wenbin Liu, Yufei Han, Yingchuan Wu, Yu Cheng, Ting Zhang, Wei Zuo
Irreversible destruction of bronchi and alveoli can lead to multiple incurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissue is one of the biggest hopes to reverse the damage and cure such diseases. Here we showed that a rare population of SOX9+ basal cells (BCs) located at airway epithelium rugae can regenerate adult human lung. Human SOX9+ BCs can be readily isolated by bronchoscopic brushing and indefinitely expanded in feeder-free condition...
January 17, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29344307/dual-turn-on-fluorescence-signal-based-controlled-release-system-for-real-time-monitoring-of-drug-release-dynamics-in-living-cells-and-tumor-tissues
#18
Xiuqi Kong, Baoli Dong, Xuezhen Song, Chao Wang, Nan Zhang, Weiying Lin
Controlled release systems with capabilities for direct and real-time monitoring of the release and dynamics of drugs in living systems are of great value for cancer chemotherapy. Herein, we describe a novel dual turn-on fluorescence signal-based controlled release system (CDox), in which the chemotherapy drug doxorubicin (Dox) and the fluorescent dye (CH) are conjugated by a hydrazone moiety, a pH-responsive cleavable linker. CDox itself shows nearly no fluorescence as the fluorescence of CH and Dox is essentially quenched by the C=N isomerization and N-N free rotation...
2018: Theranostics
https://www.readbyqxmd.com/read/29343629/the-markov-blankets-of-life-autonomy-active-inference-and-the-free-energy-principle
#19
REVIEW
Michael Kirchhoff, Thomas Parr, Ensor Palacios, Karl Friston, Julian Kiverstein
This work addresses the autonomous organization of biological systems. It does so by considering the boundaries of biological systems, from individual cells to Home sapiens, in terms of the presence of Markov blankets under the active inference scheme-a corollary of the free energy principle. A Markov blanket defines the boundaries of a system in a statistical sense. Here we consider how a collective of Markov blankets can self-assemble into a global system that itself has a Markov blanket; thereby providing an illustration of how autonomous systems can be understood as having layers of nested and self-sustaining boundaries...
January 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29343582/hiv-replication-and-latency-in-a-humanized-nsg-mouse-model-during-suppressive-oral-combinational-art
#20
Sangeetha Satheesan, Haitang Li, John C Burnett, Mayumi Takahashi, Shasha Li, Shiny Xiaqin Wu, Timothy W Synold, John J Rossi, Jiehua Zhou
Although current combinatorial antiretroviral therapy (cART) is therapeutically effective in the majority of HIV patients, interruption of therapy can cause a rapid rebound in viremia, demonstrating the existence of a stable reservoir of latently infected cells. HIV latency is therefore considered a primary barrier to HIV eradication. Identifying, quantifying, and purging the HIV reservoir is crucial to effectively curing patients and relieving them from the lifelong requirement for therapy. Latently infected transformed cell models have been used to investigate HIV latency; however, they cannot accurately represent the quiescent cellular environment of primary latently infected cells in vivo...
January 17, 2018: Journal of Virology
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