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https://www.readbyqxmd.com/read/29334224/diversity-oriented-approach-to-n-heterocyclic-compounds-from-%C3%AE-phenyl-%C3%AE-enamino-ester-via-a-mitsunobu-michael-reaction-sequence
#1
Hina P A Khan, Tushar Kanti Chakraborty
Herein we delineate a novel route for the diastereoselective construction of diversely substituted N-heterocyclic ring systems as valuable scaffolds for natural products and pharmaceuticals, starting from easily accessible prochiral α-phenyl-β-enamino ester. The reaction sequence relies on the unexplored reactivity of α-phenyl-β-enamino ester as a nucleophilic partner in Mitsunobu reaction to forge the N-tethered alkene-alcohol/thiol/amine intermediate which was subjected to intramolecular hetero-Michael addition reaction under mild conditions to furnish the respective N-heterocyclic compounds embedded with an exocyclic chiral center in high yields and excellent diastereoselectivities...
January 15, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29330773/mechanistic-regulation-of-epithelial-to-mesenchymal-transition-through-ras-signaling-pathway-and-therapeutic-implications-in-human-cancer
#2
REVIEW
Kiran Tripathi, Minal Garg
RAS effector signaling instead of being simple, unidirectional and linear cascade, is actually recognized as highly complex and dynamic signaling network. RAF-MEK-ERK cascade, being at the center of complex signaling network, links to multiple scaffold proteins through feed forward and feedback mechanisms and dynamically regulate tumor initiation and progression. Three isoforms of Ras harbor mutations in a cell and tissue specific manner. Besides mutations, their epigenetic silencing also attributes them to exhibit oncogenic activities...
January 12, 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29330730/scaffold-free-tissue-engineering-for-injured-joint-surface-restoration
#3
REVIEW
Kazunori Shimomura, Wataru Ando, Hiromichi Fujie, David A Hart, Hideki Yoshikawa, Norimasa Nakamura
Articular cartilage does not heal spontaneously due to its limited healing capacity, and thus effective treatments for cartilage injuries has remained challenging. Since the first report by Brittberg et al. in 1994, autologous chondrocyte implantation (ACI) has been introduced into the clinic. Recently, as an alternative for chondrocyte-based therapy, mesenchymal stem cell (MSC)-based therapy has received considerable research attention because of the relative ease in handling for tissue harvest, and subsequent cell expansion and differentiation...
January 5, 2018: Journal of Experimental Orthopaedics
https://www.readbyqxmd.com/read/29330711/boosting-tendon-repair-interplay-of-cells-growth-factors-and-scaffold-free-and-gel-based-carriers
#4
REVIEW
Zexing Yan, Heyong Yin, Michael Nerlich, Christian G Pfeifer, Denitsa Docheva
BACKGROUND: Tendons are dense connective tissues and critical components for the integrity and function of the musculoskeletal system. Tendons connect bone to muscle and transmit forces on which locomotion entirely depends. Due to trauma, overuse and age-related degeneration, many people suffer from acute or chronic tendon injuries. Owing to their hypovascularity and hypocellularity, tendinopathies remain a substantial challenge for both clinicians and researchers. Surgical treatment includes suture or transplantation of autograft, allograft or xenograft, and these serve as the most common technique for rescuing tendon injuries...
January 5, 2018: Journal of Experimental Orthopaedics
https://www.readbyqxmd.com/read/29324695/investigation-into-improving-the-aqueous-solubility-of-the-thieno-2-3-b-pyridine-anti-proliferative-agents
#5
Ayesha Zafar, Lisa I Pilkington, Natalie A Haverkate, Michelle van Rensburg, Euphemia Leung, Sisira Kumara, William A Denny, David Barker, Ali Alsuraifi, Clare Hoskins, Jóhannes Reynisson
It is now established that the thieno[2,3-b]pyridines are a potent class of antiproliferatives. One of the main issues encountered for their clinical application is their low water solubility. In order to improve this, two strategies were pursued. First, a morpholine moiety was tethered to the molecular scaffold by substituting the sulphur atom with nitrogen, resulting in a 1H-pyrrolo[2,3-b]pyridine core structure. The water solubility was increased by three orders of magnitude, from 1.2 µg/mL (1-thieno[2,3-b]pyridine) to 1...
January 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29323267/scaffold-free-generation-of-uniform-adipose-spheroids-for-metabolism-research-and-drug-discovery
#6
Aloysius J Klingelhutz, Francoise A Gourronc, Anna Chaly, David A Wadkins, Anthony J Burand, Kathleen R Markan, Sharon O Idiga, Meng Wu, Matthew J Potthoff, James A Ankrum
Adipose tissue dysfunction is critical to the development of type II diabetes and other metabolic diseases. While monolayer cell culture has been useful for studying fat biology, 2D culture often does not reflect the complexity of fat tissue. Animal models are also problematic in that they are expensive, time consuming, and may not completely recapitulate human biology because of species variation. To address these problems, we have developed a scaffold-free method to generate 3D adipose spheroids from primary or immortal human or mouse pre-adipocytes...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29322283/rational-design-of-engineered-microbial-cell-surface-multi-enzyme-co-display-system-for-sustainable-nadh-regeneration-from-low-cost-biomass
#7
Lei Han, Bo Liang, Jianxia Song
As an important cofactor, NADH is essential for most redox reactions and biofuel cells. However, supply of exogenous NADH is challenged, due to the low production efficiency and high cost of NADH regeneration system, as well as low stability of NADH. Here, we constructed a novel cell surface multi-enzyme co-display system with ratio- and space-controllable manner as exogenous NADH regeneration system for the sustainable NADH production from low-cost biomass. Dockerin-fused glucoamylase (GA) and glucose dehydrogenase (GDH) were expressed and assembled on the engineered bacterial surfaces, which displayed protein scaffolds with various combinations of different cohesins...
January 10, 2018: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/29315910/early-late-heterobimetallic-tantalum-rhodium-species-assembled-through-a-novel-bifunctional-nhc-oh-ligand
#8
Ravi Srivastava, Raphaël Moneuse, Julien Petit, Paul-Alexis Pavard, Vincent Dardun, Madleen Rivat, Pauline Schiltz, Marius Solari, Erwann Jeanneau, Laurent Veyre, Chloé Thieuleux, Elsje Alessandra Quadrelli, Clement Camp
The straightforward synthesis of a new unsymmetrical hydroxyl-tethered N-heterocyclic carbene (NHC) ligand, HL is presented. The free ligand exhibits an unusual OH-carbene hydrogen-bonding interaction. This OH-carbene motif is used to yield i) the first tantalum complex displaying both a Fischer-type and a Schrock-type carbene ligand and ii) a unique NHC-based early-late heterobimetallic complex. More specifically, protonolysis chemistry between the ligand hydroxyl group and imido-alkyl or alkylidene-alkyl tantalum precursors yields rare monometallic tantalum-NHC complexes, Ta(XtBu)(L)(CH2tBu)2 (X = N, CH), where the alkoxy-carbene ligand acts as a chelate...
January 9, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29315214/chitosan-cellulose-multifunctional-hydrogel-beads-design-characterization-and-evaluation-of-cytocompatibility-with-breast-adenocarcinoma-and-osteoblast-cells
#9
Poonam Trivedi, Tiina Saloranta-Simell, Uroš Maver, Lidija Gradišnik, Neeraj Prabhakar, Jan-Henrik Smått, Tamilselvan Mohan, Martin Gericke, Thomas Heinze, Pedro Fardim
Cytocompatible polysaccharide-based functional scaffolds are potential extracellular matrix candidates for soft and hard tissue engineering. This paper describes a facile approach to design cytocompatible, non-toxic, and multifunctional chitosan-cellulose based hydrogel beads utilising polysaccharide dissolution in sodium hydroxide-urea-water solvent system and coagulation under three different acidic conditions, namely 2 M acetic acid, 2 M hydrochloric acid, and 2 M sulfuric acid. The effect of coagulating medium on the final chemical composition of the hydrogel beads is investigated by spectroscopic techniques (ATR-FTIR, Raman, NMR), and elemental analysis...
January 9, 2018: Bioengineering
https://www.readbyqxmd.com/read/29313702/a-comparison-of-scaffold-free-and-scaffold-based-reconstructed-human-skin-models-as-alternatives-to-animal-use
#10
Beste Kinikoglu
Tissue engineered full-thickness human skin substitutes have various applications in the clinic and in the laboratory, such as in the treatment of burns or deep skin defects, and as reconstructed human skin models in the safety testing of drugs and cosmetics and in the fundamental study of skin biology and pathology. So far, different approaches have been proposed for the generation of reconstructed skin, each with its own advantages and disadvantages. Here, the classic tissue engineering approach, based on cell-seeded polymeric scaffolds, is compared with the less-studied cell self-assembly approach, where the cells are coaxed to synthesise their own extracellular matrix (ECM)...
December 2017: Alternatives to Laboratory Animals: ATLA
https://www.readbyqxmd.com/read/29310437/maleimide-and-cyclooctyne-based-hexakis-adducts-of-fullerene-multivalent-scaffolds-for-copper-free-click-chemistry-on-fullerenes
#11
Javier Ramos-Soriano, Jose Juan Reina, Beatriz M Illescas, Javier Rojo, Nazario Martín
The synthesis of multivalent systems based on hexakis-adducts of [60]fullerene employing a biocompatible copper-free click chemistry strategy has been accomplished. A symmetric hexakis-adduct of fullerene bearing 12 maleimide units 3 is reported and it has been employed to carry out the thiol-maleimide Michael addition. To achieve orthogonal click addition, an asymmetric derivative bearing one maleimide and ten cyclooctynes has been synthesized. The sequential and one-pot transformations of the two clickable groups have been explored, finding the best results in the case of the one-pot experiment...
January 9, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29306415/revealing-cooperative-binding-of-polycationic-cyclodextrins-with-dna-oligomers-by-capillary-electrophoresis-coupled-to-mass-spectrometry
#12
Cédric Przybylski, Juan M Benito, Véronique Bonnet, Carmen Ortiz Mellet, José M García Fernández
Gene delivery is critical for the development of nucleic acid-based therapies against a range of severe diseases. The conception of non-viral (semi)synthetic vectors with low cytotoxicity and virus-like efficiency is gathering a lot of efforts, but it represents a fantastic challenge still far from accomplishment. Carbohydrate-based scaffolds offer interesting features towards this end, such as easy availability, relatively cheap cost, tuning properties and a good biocompatibility. The lack of analytical methods providing quantitative and qualitative data on their binding properties with oligonucleotides (DNA/RNA), with a minimal time and sample consumption, represents a limitation for these channels...
March 9, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29304838/a-protocol-to-isolate-and-qualify-purified-human-preantral-follicles-in-cases-of-acute-leukemia-for-future-clinical-applications
#13
Elodie Mouloungui, Tristan Zver, Christophe Roux, Clotilde Amiot
BACKGROUND: Autotransplantation of cryopreserved ovarian cortex can be associated with a risk of cancer cell reseeding. This issue could be eliminated by grafting isolated preantral follicles. Collagenase NB6 is an enzyme produced under good manufacturing practices (GMP) in compliance with requirements for tissue engineering and transplantation in humans and thus can be used to isolate preantral follicles from ovarian tissue in the framework of further clinical applications. Multicolor flow cytometry is an effective tool to evaluate the potential contamination of follicular suspensions by leukemic cells...
January 5, 2018: Journal of Ovarian Research
https://www.readbyqxmd.com/read/29303417/evaluation-of-detergent-free-and-detergent-based-methods-for-decellularization-of-murine-skin
#14
Ali Farrokhi, Mohammadreza Pakyari, Layla Nabai, Amir Pourghadiri, Ryan Hartwell, Reza B Jalili, Aziz Ghahary
Acute and chronic wounds contribute to increased morbidity and mortality in affected people and impose significant financial burdens on healthcare systems. For these challenging wounds, Acellular Dermal Matrices (ADMs) have been used as a biological wound coverage. Unlike engineered dermal matrices, ADMs are prepared through the removal of cells from skin, while preserving the extracellular matrix structure and function. In this study, our primary objective was to develop a detergent-free method of decellularization of the skin to mitigate chemical stress on matrix molecules...
January 5, 2018: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29303201/inexpensive-multigram-scale-synthesis-of-cyclic-enamines-and-3-n-spirocyclopropyl-systems
#15
Pratik Kumar, Omar Zainul, Scott T Laughlin
Cyclic enamines are important synthons for many synthetic and pharmacological targets. Here, we report an inexpensive, catalyst-free, multigram-scale synthesis for cyclic enamines with exocyclic double bonds and four- to seven-membered rings. This strategy is more conducive to scale up, permissive of functionalization around the cyclic system, and less sensitive to the nature of the N-protecting group than previously-described methods for cyclic enamine synthesis. Further, we explore application of these enamines to the synthesis of highly-strained spirocyclic 3N-cyclopropyl scaffolds...
January 5, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29300407/acoustically-modulated-biomechanical-stimulation-for-human-cartilage-tissue-engineering
#16
Umesh S Jonnalagadda, Martyn Hill, Walid Messaoudi, Richard B Cook, Richard O C Oreffo, Peter Glynne-Jones, Rahul S Tare
Bioacoustofluidics can be used to trap and levitate cells within a fluid channel, thereby facilitating scaffold-free tissue engineering in a 3D environment. In the present study, we have designed and characterised an acoustofluidic bioreactor platform, which applies acoustic forces to mechanically stimulate aggregates of human articular chondrocytes in long-term levitated culture. By varying the acoustic parameters (amplitude, frequency sweep, and sweep repetition rate), cells were stimulated by oscillatory fluid shear stresses, which were dynamically modulated at different sweep repetition rates (1-50 Hz)...
January 4, 2018: Lab on a Chip
https://www.readbyqxmd.com/read/29300091/what-contributes-to-snris-dual-targeting-mechanism-the-key-role-of-tm6-domain-in-hsert-and-hnet-revealed-by-molecular-dynamics-simulation
#17
Weiwei Xue, Fengyuan Yang, Panpan Wang, Guoxun Zheng, Yuzong Chen, Xiaojun Yao, Feng Zhu
Dual inhibition of serotonin and norepinephrine transporters (hSERT and hNET) gives greatly improved efficacy and tolerability for treating major depressive disorder (MDD) comparing with selective reuptake inhibitors. Pioneer studies provided valuable information of structure, function, and pharmacology of drugs dual-targeting hSERT and hNET (SNRIs), and the differential binding mechanism between SNRIs and selective inhibitors of 5-HT (SSRIs) / NE (sNRIs) to their corresponding target was expected to be able to facilitate the discovery of privileged drug-like scaffold with improved efficacy...
January 4, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29289571/crystalline-paclitaxel-coated-des-with-bioactive-protective-layer-development
#18
Shady Farah, Abraham J Domb
Drug eluting stents (DES) based on polymeric-carriers currently lead the market, however, reports on clinical complications encourage the development of safer and more effective DES. We recently reported on carrier-free DES based on rapamycin crystalline coating as a potential therapeutic solution. Here, we report for the first time surface crystallization of paclitaxel (PT) onto metallic stents. The physicochemical principles of crystallization and key process parameters were extensively studied for fabrication of controllable and homogeneous crystalline coatings on stent scaffolds...
December 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29283220/recent-advances-in-extrusion-based-3d-printing-for-biomedical-applications
#19
REVIEW
Jesse K Placone, Adam J Engler
Additive manufacturing, or 3D printing, has become significantly more commonplace in tissue engineering over the past decade, as a variety of new printing materials have been developed. In extrusion-based printing, materials are used for applications that range from cell free printing to cell-laden bioinks that mimic natural tissues. Beyond single tissue applications, multi-material extrusion based printing has recently been developed to manufacture scaffolds that mimic tissue interfaces. Despite these advances, some material limitations prevent wider adoption of the extrusion-based 3D printers currently available...
December 28, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29283208/microphysiological-analysis-platform-of-pancreatic-islet-%C3%AE-cell-spheroids
#20
Sang Hun Lee, SoonGweon Hong, Jihwan Song, Byungrae Cho, Esther J Han, Sravani Kondapavulur, Dongchoul Kim, Luke P Lee
The hallmarks of diabetics are insufficient secretion of insulin and dysregulation of glucagon. It is critical to understand release mechanisms of insulin, glucagon, and other hormones from the islets of Langerhans. In spite of remarkable advancements in diabetes research and practice, robust and reproducible models that can measure pancreatic β-cell function are lacking. Here, a microphysiological analysis platform (MAP) that allows the uniform 3D spheroid formation of pancreatic β-cell islets, large-scale morphological phenotyping, and gene expression mapping of chronic glycemia and lipidemia development is reported...
December 28, 2017: Advanced Healthcare Materials
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