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https://www.readbyqxmd.com/read/28817816/exosomes-derived-from-human-bone-marrow-mesenchymal-stem-cells-promote-tumor-growth-through-hedgehog-signaling-pathway
#1
Jin Qi, Yali Zhou, Zuoyi Jiao, Xu Wang, Yang Zhao, Yangbin Li, Huijuan Chen, Luxi Yang, Hongwen Zhu, Yumin Li
BACKGROUND/AIMS: Mesenchymal stem/stromal cells (MSCs) are known to home to sites of tumor microenvironments where they participate in the formation of the tumor microenvironment and to interplay with tumor cells. However, the potential functional effects of MSCs on tumor cell growth are controversial. Here, we, from the view of bone marrow MSC-derived exosomes, study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells. METHODS: MSCs derived from human bone marrow (hBMSCs) were isolated and cultured in complete DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin, cell culture supernatants containing exosomes were harvested and exosome purification was performed by ultracentrifugation...
August 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28817722/nicotinamide-alone-accelerates-the-conversion-of-mouse-embryonic-stem-cells-into-mature-neuronal-populations
#2
Síle M Griffin, Mark R Pickard, Rowan P Orme, Clive P Hawkins, Adrian C Williams, Rosemary A Fricker
INTRODUCTION: Vitamin B3 has been shown to play an important role during embryogenesis. Specifically, there is growing evidence that nicotinamide, the biologically active form of vitamin B3, plays a critical role as a morphogen in the differentiation of stem cells to mature cell phenotypes, including those of the central nervous system (CNS). Detailed knowledge of the action of small molecules during neuronal differentiation is not only critical for uncovering mechanisms underlying lineage-specification, but also to establish more effective differentiation protocols to obtain clinically relevant cells for regenerative therapies for neurodegenerative conditions such as Huntington's disease (HD)...
2017: PloS One
https://www.readbyqxmd.com/read/28817258/synthesis-of-complex-glycolates-by-enantioconvergent-addition-reactions
#3
Samuel L Bartlett, Jeffrey S Johnson
The unique role that stereochemistry plays in molecular recognition events continues to provide a driving force for synthesizing organic compounds in enantioenriched form. The tendency of enantioenriched organic compounds to revert to an entropically favored racemic state in the presence of viable racemization pathways (e.g., the enolization of stereogenic carbonyl derivatives) can sometimes interfere with this objective; however, beginning with Noyori's foundational disclosure of a dynamic kinetic transfer hydrogenation, the ability to channel racemic, configurationally labile starting materials through stereoconvergent reaction pathways has been recognized as a powerful strategy in asymmetric synthesis...
August 17, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28817257/cation-anion-arrangement-patterns-in-self-assembled-pd2l4-and-pd4l8-coordination-cages
#4
Guido H Clever, Philip Punt
Compounds featuring one-dimensional regular arrangements of stacked metal complexes and alternating [cation-anion]∞ sequences have raised considerable interest owing to their peculiar electronic and optical properties as well as guest inclusion capabilities. While traditional ways to realize these structural motifs rely on crystalline compounds, exclusively existing in the solid state, recent progress in the area of metal-mediated supramolecular self-assembly allows for the rational synthesis of structurally well-defined short stretches of stacked metal complexes and cation-anion arrangements...
August 17, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28817181/introduction-of-hsa-mir-103a-and-hsa-mir-1827-and-hsa-mir-137-as-new-regulators-of-wnt-signaling-pathway-and-their-relation-to-colorectal-carcinoma
#5
Ali Fasihi, Bahram M Soltani, Amir Atashi, Shirzad Nasiri
Wnt signaling is hyper-activated in most of human cancers including colorectal carcinoma (CRC). Therefore, the introduction of new regulators for Wnt pathway possesses promising diagnostic and therapeutic applications in cancer medicine. Bioinformatics analysis introduced hsa-miR-103a, hsa-miR-1827, and hsa-miR-137 as potential regulators of Wnt signaling pathway. Here, we intended to examine the effect of these human miRNAs on Wnt signaling pathway components, on the cell cycle progression in CRC originated cell lines and their expression in CRC tissues...
August 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28817175/drug-development-for-breast-colorectal-and-non-small-cell-lung-cancers-from-1979-to-2014
#6
Nancy A Nixon, Omar F Khan, Hasiba Imam, Patricia A Tang, Jose Monzon, Haocheng Li, Gavin Sun, Doreen Ezeife, Sunil Parimi, Scot Dowden, Vincent C Tam
BACKGROUND: Understanding the drug development pathway is critical for streamlining the development of effective cancer treatments. The objective of the current study was to delineate the drug development timeline and attrition rate of different drug classes for common cancer disease sites. METHODS: Drugs entering clinical trials for breast, colorectal, and non-small cell lung cancer were identified using a pharmaceutical business intelligence database. Data regarding drug characteristics, clinical trials, and approval dates were obtained from the database, clinical trial registries, PubMed, and regulatory Web sites...
August 17, 2017: Cancer
https://www.readbyqxmd.com/read/28817152/gradient-free-determination-of-isoelectric-points-of-proteins-on-chip
#7
Urszula Łapińska, Kadi L Saar, Emma V Yates, Therese W Herling, Thomas Müller, Pavan K Challa, Christopher M Dobson, Tuomas P J Knowles
The isoelectric point (pI) of a protein is a key characteristic that influences its overall electrostatic behaviour. The majority of conventional methods for the determination of the isoelectric point of a molecule rely on the use of spatial gradients in pH, although significant practical challenges are associated with such techniques, notably the difficulty in generating a stable and well controlled pH gradient. Here, we introduce a gradient-free approach, exploiting a microfluidic platform which allows us to perform rapid pH change on chip and probe the electrophoretic mobility of species in a controlled field...
August 17, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28816379/from-enzymes-to-functional-materials-towards-activation-of-small-molecules
#8
Frauke Möller, Stefan Piontek, Reece G Miller, Ulf-Peter Apfel
The design of non-noble metal containing heterogenous catalysts for the activation of small molecules is of utmost importance for our society. While nature possesses very sophisticated machineries to perform such conversions, rationally designed catalytic materials are rare. Herein, we aim to raise the awareness of the overall common design and working principles of catalysts and "break down the boundaries" between biology, chemistry and material sciences.
August 17, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28816232/dual-roles-of-qoa-8a-in-antiosteoporosis-a-combination-of-bone-anabolic-and-anti-resorptive-effects
#9
Jing Wu, Qi Shen, Wei Cui, Yu Zhao, Yue Huai, Yu-Chao Zhang, Bei-Hua Bao, Chen-Xi Liu, Qing Jiang, Jian-Xin Li
Osteoporotic treatments have largely depended on antiresorptive or anabolic drugs; but the former also suppresses new bone formation, and the latter only includes human parathyroid hormone. There is no drug that has a dual effect to inhibit bone resorption and to stimulate bone formation simultaneously. Here, we report a small molecule, a quinoxaline derivative of oleanolic acid (QOA-8a) that plays such dual roles in osteoblasts and osteoclasts in the treatment of osteoporosis. Osteoclast differentiation was induced by incubation of primary mouse bone marrow-derived macrophages in the presence of RANKL and M-CSF, treatment with QOA-8a dose-dependently inhibited the osteoclast formation with an IC50 value of 0...
August 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28816051/lipid-stabilized-water-oil-interfaces-studied-by-micro-focusing-small-angle-x-ray-scattering
#10
Emanuela Di Cola, Kristian Torbensen, Ilaria Clemente, Federico Rossi, Sandra Ristori, Ali Abou-Hassan
Water in oil (w/o) simple emulsions are dispersed micro-confined systems which find applications in many areas of advanced materials and biotechnology, such as food industry, drug delivery and cosmetics, to name but a few. In these systems, the structural and chemical properties of the boundary layer at the w/o interface are of paramount importance to determine functionality and stability. Recently, microfluidic methods have emerged as a valuable tool to fabricate monodisperse emulsion droplets. Due to the intrinsic flexibility of microfluidics, different interfaces can be obtained, and general principles governing the interfacial stability are needed to guide the experimental approach...
August 17, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28815832/targeting-the-genome-stability-hub-ctf4-by-stapled-peptide-design
#11
Yuteng Wu, Fabrizio Villa, Joseph Maman, Lina Dobnikar, Yu H Lau, Aline C Simon, Karim Labib, David R Spring, Luca Pellegrini
Exploitation of synthetic lethality by small-molecule targeting of pathways that maintain genomic stability is an attractive chemotherapeutic approach. The Ctf4/AND-1 protein hub that links DNA replication, repair and chromosome segregation, represents a novel target for the synthetic lethality approach. Here we report the design, optimization, and validation of double-click stapled peptides encoding the Ctf4-interacting peptide (CIP) of the replicative helicase subunit Sld5. Screening stapling positions in the Sld5 CIP, we identified an unorthodox i,i+6 stapled peptide with improved, sub-micromolar binding to Ctf4...
August 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28815828/exploring-electrical-currents-through-nanographenes-visualization-and-tuning-of-the-through-bond-transmission-paths
#12
Thijs Stuyver, Nathalie Blotwijk, Stijn Fias, Paul Geerlings, Frank De Proft
In this work, electrical currents through nanographenes, a class of alternant hydrocarbons also known as polycyclic aromatic hydrocarbons, in molecular junctions under small bias are explored. We illustrate that when the π-current dominates, i.e. when no quantum interference takes place, the current prefers the direction of the shortest bond (the bond with the highest double bond character) upon entering the molecule from the contacts. As such, the idea of electrons propagating through double bonds from contact to contact, originating from the curly arrow drawings used in a previously established selection rule for transmission, seems to be more deeply rooted in the actual physical process of electron transport than previously anticipated...
August 16, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/28815586/differential-interference-contrast-photothermal-microscopy-in-nanospace-impacts-of-systematic-parameters
#13
M Liu
Differential interference contrast-photothermal microscopy (DIC-PTM), as a promising tool for trace analysis of nonfluorescent compounds, suffered low sensitivity in nanospace especially for aqueous samples, due to the poor thermophysical property of water and the unoptimised configuration. To improve its performance, a five-layer DIC-PTM model is built and influences of different parameters on the photothermal signal are investigated. The initial phase shift φ0 between two branches of the probe beam is found to be a key factor determining the detection sensitivity and response linearity: at a large φ0 (≤π/2) both a high sensitivity and a good linearity can be achieved, while a high signal-to-noise ratio occurs at a small φ0 ...
August 16, 2017: Journal of Microscopy
https://www.readbyqxmd.com/read/28815537/from-heterochromatin-to-long-noncoding-rnas-in-drosophila-expanding-the-arena-of-gene-function-and-regulation
#14
Subhash C Lakhotia
Recent years have witnessed a remarkable interest in exploring the significance of pervasive noncoding transcripts in diverse eukaryotes. Classical cytogenetic studies using the Drosophila model system unraveled the perplexing attributes and "functions" of the "gene"-poor heterochromatin. Recent molecular studies in the fly model are likewise revealing the very diverse and significant roles played by long noncoding RNAs (lncRNAs) in development, gene regulation, chromatin organization, cell and nuclear architecture, etc...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28815237/induced-polarization-restricts-the-conformational-distribution-of-a-light-harvesting-molecular-triad-in-the-ground-state
#15
Oleg N Starovoytov, Pengzhi Zhang, Piotr Cieplak, Margaret S Cheung
The light-harvesting molecular triad consisting of carotenoid polyene (C), diaryl-porphyrin (P) and pyrrole-fullerene (C60) is a donor-acceptor molecule capable of absorbing incident light in the visible range. Its ability to convert solar energy to electrical excitation and charge separation energy suggests a great potential in real-world applications. The ensemble of its conformations under ambient conditions varies widely according to its electronic state. In previous work, we applied a non-polarizable model to study the conformational distribution of the molecular triad in the ground and charge separated states...
August 17, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28815227/microparticle-parking-and-isolation-for-highly-sensitive-microrna-detection
#16
Jae Jung Kim, Lynna Chen, Patrick S Doyle
Isolating small objects, such as particles, cells, and molecules, in individual aqueous droplets is useful for chemical and biological assays. We have developed a simple microfluidic platform to immobilize (park) microparticles at defined locations, and isolate particles in monodisperse droplets surrounded by immiscible oil. While conventional methods can only achieve stochastic encapsulation of objects within larger droplets, our in situ method ensures that a single particle is entrapped in a similar-sized droplet, with ∼95% yield for parking and isolation...
August 17, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28815109/visualization-of-molecular-structures-using-hololens-based-augmented-reality
#17
M A Hoffman, J B Provance
Biological molecules and biologically active small molecules are complex three dimensional structures. Current flat screen monitors are limited in their ability to convey the full three dimensional characteristics of these molecules. Augmented reality devices, including the Microsoft HoloLens, offer an immersive platform to change how we interact with molecular visualizations. We describe a process to incorporate the three dimensional structures of small molecules and complex proteins into the Microsoft HoloLens using aspirin and the human leukocyte antigen (HLA) as examples...
2017: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/28814804/a-unique-thermo-induced-gel-to-gel-transition-in-a-ph-sensitive-small-molecule-hydrogel
#18
Hongtao Xie, Mehran Asad Ayoubi, Wensheng Lu, Jide Wang, Jianbin Huang, Wei Wang
For a hydrogel based on a zwitterionic dendritic surfactant, we report an apparently unprecedented reversible temperature-induced gel-to-gel phase transition below the melting point of its alkyl chains, where the supramolecular self-assembly of surfactant molecules underwent a dramatic transformation from low-temperature surfactant bilayers to high-temperature entangled surfactant worm-like micelles.
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814738/identification-of-novel-non-secosteroidal-vitamin-d-receptor-agonists-with-potent-cardioprotective-effects-and%C3%A2-%C3%AF-%C3%AF-devoid-of-hypercalcemia
#19
Santosh A Khedkar, Mohammed A Samad, Sangita Choudhury, Ji Yoo Lee, Dongsheng Zhang, Ravi I Thadhani, S Ananth Karumanchi, Alan C Rigby, Peter M Kang
Vitamin D regulates many biological processes, but its clinical utility is limited by its hypercalcemic effect. Using a virtual screening platform to search novel chemical probes that activate the vitamin D signaling, we report discovery of novel non-steroidal small-molecule compounds that activate the vitamin D receptor (VDR), but are devoid of hypercalcemia. A lead compound (known as VDR 4-1) demonstrated potent transcriptional activities in a VDR reporter gene assay, and significantly ameliorated cardiac hypertrophy in cell culture studies and in animal models...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814721/acceleration-of-osteoblast-differentiation-by-a-novel-osteogenic-compound-dmp-pyt-through-activation-of-both-the-bmp-and-wnt-pathways
#20
Su Jung Bae, Hye Joo Kim, Hee Yeon Won, Yong Ki Min, Eun Sook Hwang
Osteoblast differentiation is regulated through the successive activation of signaling molecules by a complex interplay of extracellular signals such as bone morphogenetic protein (BMP) and Wnt ligands. Numerous studies have identified natural as well as synthetic compounds with osteogenic activity through the regulation of either BMP/SMADs or the Wnt/β-catenin pathway. Here, we attempted to isolate small molecules that concurrently activated both SMADs and β-catenin, which led to the discovery of a novel potent osteogenic compound, DMP-PYT...
August 16, 2017: Scientific Reports
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