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https://www.readbyqxmd.com/read/28548833/structure-activity-relationship-for-small-molecule-inhibitors-of-nicotinamide-n-methyltransferase
#1
Harshini Neelakantan, Hua-Yu Wang, Virginia Vance, Jonathan D Hommel, Stanton F McHardy, Stanley J Watowich
Nicotinamide N-methyltransferase (NNMT) is a fundamental cytosolic biotransforming enzyme that catalyzes the N-methylation of endogenous and exogenous xenobiotics. We have identified small molecule inhibitors of NNMT with >1000-fold range of activity and developed comprehensive structure-activity relationships (SARs) for NNMT inhibitors. Screening of N-methylated quinolinium, isoquinolinium, pyrididium, and benzimidazolium/benzothiazolium analogs resulted in the identification of quinoliniums as a promising scaffold with very low micromolar (IC50 ~1 μM) NNMT inhibition...
May 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28548695/development-of-a-novel-bioabsorbable-implant-that-is-substituted-by-adipose-tissue-in-vivo
#2
Shuichi Ogino, Naoki Morimoto, Michiharu Sakamoto, Chizuru Jinno, Katsuhiro Yoshikawa, Tatsuki Enoshiri, Yuki Sakamoto, Tsuguyoshi Taira, Shigehiko Suzuki
Recently, adipose tissue has been regenerated by combining scaffolds, growth factors, and/or adipose tissue-derived stromal cells (ASCs). However, the safety of growth factors and ASCs has not been confirmed in cancer patients. We reported the regeneration of adipose tissue in the internal space of a polypropylene mesh containing a collagen sponge (CS), without using any growth factors or cells. We herein explored the formation of adipose tissue, using the bioabsorbable implant containing CS, in rats. We prepared the implants without and with CS, using threads of either poly l-lactide-co-ε-caprolactone [P(LA/CL)] or poly-l-lactic acid (PLLA), and measured their strengths...
May 26, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28548666/zinc-and-the-iron-donor-frataxin-regulate-oligomerization-of-the-scaffold-protein-to-form-new-fe-s-cluster-assembly-centers
#3
B K Galeano, W Ranatunga, O Gakh, D Y Smith, J R Thompson, G Isaya
Early studies of the bacterial Fe-S cluster assembly system provided structural details for how the scaffold protein and the cysteine desulfurase interact. This work and additional work on the yeast and human systems elucidated a conserved mechanism for sulfur donation but did not provide any conclusive insights into the mechanism for iron delivery from the iron donor, frataxin, to the scaffold. We previously showed that oligomerization is a mechanism by which yeast frataxin (Yfh1) can promote assembly of the core machinery for Fe-S cluster synthesis both in vitro and in cells, in such a manner that the scaffold protein, Isu1, can bind to Yfh1 independent of the presence of the cysteine desulfurase, Nfs1...
May 26, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28548628/endothelial-progenitor-cells-for-the-vascularization-of-engineered-tissues
#4
Erica Brown Peters
Self-assembled microvasculature from cocultures of endothelial cells and stromal cells have significantly advanced efforts to vascularize engineered tissues by enhancing perfusion rates <i>in vivo</i> and producing investigative platforms for microvascular morphogenesis <i>in vitro</i>. However, in order to clinically translate prevascularized constructs, the issue of endothelial cell source must be resolved. Endothelial progenitor cells (EPCs) can be noninvasively supplied from the recipient through adult peripheral and umbilical cord blood, as well as derived from induced pluripotent stem cells, alleviating antigenicity issues...
May 26, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/28548569/thyroxine-increases-collagen-type-ii-expression-and-accumulation-in-scaffold-free-tissue-engineered-articular-cartilage
#5
G Adam Whitney, Thomas J Kean, Russell J Fernandes, Stephen D Waldman, M Yat Tse, Stephen C Pang, Joseph M Mansour, James E Dennis
Low collagen accumulation in the extra-cellular matrix is a pressing problem in cartilage tissue engineering, leading to a low collagen-to-glycosaminoglycan (GAG) ratio and poor mechanical properties in neo-cartilage. Soluble factors have been shown to increase collagen content, but may result in a more pronounced increase in GAG content. Thyroid hormones have been reported to stimulate collagen and GAG production, but reported outcomes, including which specific collagen types are affected, are variable throughout the literature...
May 26, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28548499/polyoxovanadate-alkoxide-clusters-as-a-redox-reservoir-for-iron
#6
Feng Li, Stephanie H Carpenter, Robert F Higgins, Mark G Hitt, William W Brennessel, Maryline G Ferrier, Samantha K Cary, Juan S Lezama-Pacheco, Joshua T Wright, Benjamin W Stein, Matthew P Shores, Michael L Neidig, Stosh A Kozimor, Ellen M Matson
Inspired by the multielectron redox chemistry achieved using conventional organic-based redox-active ligands, we have characterized a series of iron-functionalized polyoxovanadate-alkoxide clusters in which the metal oxide scaffold functions as a three-dimensional, electron-deficient metalloligand. Four heterometallic clusters were prepared through sequential reduction, demonstrating that the metal oxide scaffold is capable of storing up to four electrons. These reduced products were characterized by cyclic voltammetry, IR, electronic absorption, and (1)H NMR spectroscopies...
May 26, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28548311/multivalency-to-inhibit-and-discriminate-hexosaminidases
#7
Yves Bleriot, Dimitri Alvarez-Dorta, Dustin T King, Thibaut Legigan, Daisuke Ide, Isao Adachi, David Deniaud, Jerome Desire, Atsushi Kato, David Vocadlo, Sebastien Gouin
A set of multivalent polyhydroxylated acetamidoazepanes based on ethylene glycol, glucoside or cyclodextrin scaffolds was prepared. The compounds were assessed against plant, mammalian and therapeutically relevant hexosaminidases. Multimerization was shown to improve the inhibitory potency with synergy, and to fine tune the selectivity profile between related hexosaminidases.
May 26, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28548246/comparison-of-three-different-types-of-scaffolds-preseeded-with-human-bone-marrow-mononuclear-cells-on-the-bone-healing-in-a-femoral-critical-size-defect-model-of-the-athymic-rat
#8
Maren Janko, Julian Sahm, Alexander Schaible, Jan C Brune, Marlene Bellen, Katrin Schröder, Caroline Seebach, Ingo Marzi, Dirk Henrich
Large bone defects often pose major difficulties in orthopedic surgery. The application of long term cultured stem cells combined with a scaffold lead to a significant improvement of bone healing in recent experiments but is strongly restricted by EU-law. Bone marrow mononuclear cells (BMC), however, can be isolated and transplanted within few hours and have been proven effective in experimental models of bone healing. The effectivity of the BMC supported therapy might be influenced by the type of scaffold...
May 26, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28548149/fluorous-tag-assisted-synthesis-of-bile-acid-bisphosphonate-conjugates-via-orthogonal-click-reactions-an-access-to-potential-anti-resorption-bone-drugs
#9
Chiara Massarenti, Olga Bortolini, Giancarlo Fantin, Dario Cristofaro, Daniele Ragno, Daniela Perrone, Elena Marchesi, Gianluca Toniolo, Alessandro Massi
The synthesis of a small collection of novel bile acid-bisphosphonate (BA-BP) conjugates as potential drug candidates is reported. The disclosed methodology relied on the installation of azide and thiol functionalities at the head and tail positions, respectively, of the BA scaffold and its subsequent decoration by orthogonal click reactions (copper-catalyzed azide-alkyne cycloaddition, thiol-ene or thiol-yne coupling) to introduce BP units and a fluorophore. Because of the troublesome isolation of the target conjugates by standard procedures, the methodology culminated with the functionalization of the BA scaffold with a light fluorous tag to rapidly and efficiently purify intermediates and final products by fluorous solid-phase extraction...
May 26, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28548098/rationally-designed-mineralization-for-selective-recovery-of-the-rare-earth-elements
#10
Takaaki Hatanaka, Akimasa Matsugami, Takamasa Nonaka, Hideki Takagi, Fumiaki Hayashi, Takao Tani, Nobuhiro Ishida
The increasing demand for rare earth (RE) elements in advanced materials for permanent magnets, rechargeable batteries, catalysts and lamp phosphors necessitates environmentally friendly approaches for their recovery and separation. Here, we propose a mineralization concept for direct extraction of RE ions with Lamp (lanthanide ion mineralization peptide). In aqueous solution containing various metal ions, Lamp promotes the generation of RE hydroxide species with which it binds to form hydrophobic complexes that accumulate spontaneously as insoluble precipitates, even under physiological conditions (pH ∼6...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28547848/effect-of-ceramic-calcium-phosphorus-ratio-on-chondrocyte-mediated-biosynthesis-and-mineralization
#11
Margaret K Boushell, Nora T Khanarian, Raquel Z LeGeros, Helen H Lu
The osteochondral interface functions as a structural barrier between cartilage and bone, maintaining tissue integrity post injury and during homeostasis. Regeneration of this calcified cartilage region is thus essential for integrative cartilage healing, and hydrogel-ceramic composite scaffolds have been explored for calcified cartilage formation. The objective of this study is to test the hypothesis that Ca/P ratio of the ceramic phase of the composite scaffold regulates chondrocyte biosynthesis and mineralization potential...
May 25, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28547835/application-of-omentum-as-an-in-vivo-bioreactor-for-regeneration-of-decellularized-human-internal-mammary-artery
#12
Reza Khorramirouz, Maryam Kameli, Sahar Eftekharzadeh, Abdol-Mohammad Kajbafzadeh
This study investigates the extent of cell seeding as well as lumen patency in acellular Internal mammary artery (IMA) scaffolds that have been re-cellularized by omentum as a natural bioreactor. Sixteen Virgin female Wistar rats were selected for implantation of acellular scaffold in omentum. Following laparotomy omentum was retracted to the outside of the abdomen and the more vascularized portion of it was selected for the experiment. The scaffold was wrapped by omentum and placed between two layers of rectus muscles that have been previously dissected...
May 25, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28547816/three-component-aminoalkylations-yielding-dihydronaphthoxazine-based-sirtuin-inhibitors-scaffold-modification-and-exploration-of-space-for-polar-side-chains
#13
Steffen Vojacek, Katja Beese, Zayan Alhalabi, Sören Swyter, Anja Bodtke, Carola Schulzke, Manfred Jung, Wolfgang Sippl, Andreas Link
Nonpolar derivatives of heterocyclic aromatic screening hits like the non-selective sirtuin inhibitor splitomicin tend to be poorly soluble in biological fluids. Unlike sp(3) -rich natural products, flat aromatic compounds are prone to stacking and often difficult to optimize into leads with activity in cellular systems. The aim of this work was to identify anchor points for the introduction of sp(3) -rich fragments with polar functional groups into the newly discovered active (IC50  = 5 μM) but nonpolar scaffold 1,2-dihydro-3H-naphth[1,2-e][1,3]oxazine-3-thione by a molecular modeling approach...
May 26, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28547791/an-organoruthenium-anticancer-agent-shows-unexpected-target-selectivity-for-plectin
#14
Samuel M Meier, Dominique Kreutz, Lilli Winter, Matthias H M Klose, Klaudia Cseh, Tamara Weiss, Andrea Bileck, Beatrix Alte, Johanna C Mader, Samir Jana, Annesha Chatterjee, Arindam Bhattacharyya, Michaela Hejl, Michael A Jakupec, Petra Heffeter, Walter Berger, Christian G Hartinger, Bernhard K Keppler, Gerhard Wiche, Christopher Gerner
Organometallic metal(arene) anticancer agents require ligand exchange for their anticancer activity and this is generally believed to confer low selectivity for potential cellular targets. However, using an integrated proteomics-based target-response profiling approach as a potent hypothesis-generating procedure, we found an unexpected target selectivity of a ruthenium(arene) pyridinecarbothioamide (plecstatin) for plectin, a scaffold protein and cytolinker, which was validated in a plectin knock-out model in vitro...
May 26, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28547582/ran-binding-protein-9-ranbpm-binds-ifn-%C3%AE-r1-in-the-ifn-%C3%AE-signaling-pathway
#15
Junwen Zhang, Xiaojie Cong, Jiajie Zhaoqiao, Xia Yang, Meng Li, Hong Chen, Ruifang Mi, Guishan Jin, Fusheng Liu, Bing-Ren Huang
Like the type I interferons (IFNs), the recently discovered cytokine IFN-λ displays antiviral, antiproliferative, and proapoptotic activities, mediated by a heterodimeric IFN-λ receptor complex composed of a unique IFN-λR1 chain and the IL-10R2 chain. However, the molecular mechanism of the IFN-λ-regulated pathway remains unclear. In this study, we newly identified RAN-binding protein M (RanBPM) as a binding partner of IFN-λR1. The interaction between RanBPM and IFN-λR1 was identified with a glutathione S-transferase pull-down assay and coimmunoprecipitation experiments...
May 24, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28546566/a-diastereoselective-synthesis-of-cebranopadol-a-novel-analgesic-showing-nop-mu-mixed-agonism
#16
Anna Fantinati, Sara Bianco, Remo Guerrini, Severo Salvadori, Salvatore Pacifico, Maria Camilla Cerlesi, Girolamo Calo, Claudio Trapella
A diastereoselective synthesis of the title compound as a single E diastereomer has been efficiently accomplished by assembling the featured pyrano-indole scaffold of the spiro[cyclohexane-dihydropyrano[3,4-b]-indole]-amine framework through an oxa-Pictet-Spengler reaction, promoted by a cheap and green Zeolite catalyst. Basic pharmacological experiments demonstrate that Cebranopadol acts as a mixed nociception/orphanin FQ (NOP) and mu (MOP) opioid receptor agonist useful for treatment of chronic pain.
May 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28546478/draft-genome-sequence-of-the-mycoparasitic-oomycete-pythium-oligandrum-strain-cbs-530-74
#17
Sandeep K Kushwaha, Ramesh R Vetukuri, Laura J Grenville-Briggs
The oomycete Pythium oligandrum is a mycoparasite and licenced biological control agent. Here, we report the draft genome sequence of P. oligandrum strain CBS 530.74, which is 36.80 Mb. It contains 341 scaffolds and 11,647 predicted protein-coding genes. As reported for plant-pathogenic Pythium species, RXLR-type effector sequences are absent.
May 25, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28546385/using-rna-seq-for-genomic-scaffold-placement-correcting-assemblies-and-genetic-map-creation-in-a-common-brassica-rapa-mapping-population
#18
R J Cody Markelz, Michael F Covington, Marcus T Brock, Upendra K Devisetty, Daniel J Kliebenstein, Cynthia Weinig, Julin N Maloof
Brassica rapa is a model species for agronomic, ecological, evolutionary and translational studies. Here we describe high-density SNP discovery and genetic map construction for a Brassica rapa recombinant inbred line (RIL) population derived from field collected RNA-seq data. This high-density genotype data enables the detection and correction of putative genome mis-assemblies and accurate assignment of scaffold sequences to their likely genomic locations. These assembly improvements represent 7.1-8.0% of the annotated Brassica rapa genome...
May 25, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28546133/tissue-engineered-trachea-regeneration-using-decellularized-trachea-matrix-treated-with-laser-micropore-technique
#19
Yong Xu, Dan Li, Zongqi Yin, Aijuan He, Miaomiao Lin, Gening Jiang, Xiao Song, Xuefei Hu, Yi Liu, Jinpeng Wang, Xiaoyun Wang, Liang Duan, Guangdong Zhou
Tissue-engineered trachea provides a promising approach for reconstruction of long segmental tracheal defects. However, a lack of ideal biodegradable scaffolds greatly restricts its clinical translation. Decellularized trachea matrix (DTM) is considered a proper scaffold for trachea cartilage regeneration owing to natural tubular structure, cartilage matrix components, and biodegradability. However, cell residual and low porosity of DTM easily result in immunogenicity and incomplete cartilage regeneration. To address these problems, a laser micropore technique (LMT) was applied in the current study to modify trachea sample porosity to facilitate decellular treatment and cell ingrowth...
May 22, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28546035/hybrid-metal-scaffold-jacket-versus-full-metal-jackets-in-left-anterior-descending-coronary-artery-diffuse-disease-differences-in-radiation-exposure-and-fluoroscopic-procedural-times
#20
Gianluca Rigatelli, Marco Zuin, Jacopo Frigato, Fabio Dell'Avvocata, Federico Ronco, Alberto Mazza, Laura Oliva, Dario Adami, Emiliano Bedendo, Panin Stefano
BACKGROUND/PURPOSE: Bioabsorbable vascular scaffolds (BVS) are made from a radiolucent material. Their multiple implantations on a single long diffused segment requires a specific technique with imaging magnification, which could cause an increase in dose delivered during percutaneous coronary intervention (PCI) procedure. We aimed to identify differences in radiation dose, fluoroscopy and procedural times in Hybrid DES+ multiple BVS (Absorb, Abbott Inc., USA) implantation (hybrid metal/scaffold jacket) versus multiple III generation Drug-eluting stents (DES) (full-metal jacket) in patients with long and diffuse coronary artery disease of the left anterior descending (LAD) coronary artery...
May 18, 2017: Cardiovascular Revascularization Medicine: Including Molecular Interventions
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