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https://www.readbyqxmd.com/read/28239758/acellular-mouse-kidney-ecm-can-be-used-as-a-three-dimensional-substrate-to-test-the-differentiation-potential-of-embryonic-stem-cell-derived-renal-progenitors
#1
Manpreet Sambi, Theresa Chow, Jennifer Whiteley, Mira Li, Shawn Chua, Vanessa Raileanu, Ian M Rogers
The development of strategies for tissue regeneration and bio-artificial organ development is based on our understanding of embryogenesis. Differentiation protocols attempt to recapitulate the signaling modalities of gastrulation and organogenesis, coupled with cell selection regimens to isolate the cells of choice. This strategy is impeded by the lack of optimal in vitro culture systems since traditional culture systems do not allow for the three-dimensional interaction between cells and the extracellular matrix...
February 27, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28239443/enantioselective-convergent-synthesis-of-the-ineleganolide-core-by-a-tandem-annulation-cascade
#2
Robert A Craig, Jennifer L Roizen, Russell C Smith, Amanda C Jones, Scott C Virgil, Brian M Stoltz
An enantioselective and diastereoselective approach toward the synthesis of the polycyclic norditerpenoid ineleganolide is disclosed. A palladium-catalyzed enantioselective allylic alkylation is employed to stereoselectively construct the requisite chiral tertiary ether and facilitate the synthesis of a 1,3-cis-cyclopentenediol building block. Careful substrate design enabled the convergent assembly of the ineleganolide [6,7,5,5]-tetracyclic scaffold by a diastereoselective cyclopropanation-Cope rearrangement cascade under unusually mild conditions...
January 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28238143/electrospun-nanofiber-scaffolds-and-their-hydrogel-composites-for-the-engineering-and-regeneration-of-soft-tissues
#3
Ohan S Manoukian, Rita Matta, Justin Letendre, Paige Collins, Augustus D Mazzocca, Sangamesh G Kumbar
Electrospinning has emerged as a simple, elegant, and scalable technique that can be used to fabricate polymeric nanofibers. Pure polymers as well as blends and composites of both natural and synthetic ones have been successfully electrospun into nanofiber matrices for many biomedical applications. Tissue-engineered medical implants, such as polymeric nanofiber scaffolds, are potential alternatives to autografts and allografts, which are short in supply and carry risks of disease transmission. These scaffolds have been used to engineer various soft tissues, including connective tissues, such as skin, ligament, and tendon, as well as nonconnective ones, such as vascular, muscle, and neural tissue...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28230077/cartilage-like-electrostatic-stiffening-of-responsive-cryogel-scaffolds
#4
G S Offeddu, I Mela, P Jeggle, R M Henderson, S K Smoukov, M L Oyen
Cartilage is a structural tissue with unique mechanical properties deriving from its electrically-charged porous structure. Traditional three-dimensional environments for the culture of cells fail to display the complex physical response displayed by the natural tissue. In this work, the reproduction of the charged environment found in cartilage is achieved using polyelectrolyte hydrogels based on polyvinyl alcohol and polyacrylic acid. The mechanical response and morphology of microporous physically-crosslinked cryogels are compared to those of heat-treated chemical gels made from the same polymers, as a result of pH-dependent swelling...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228228/molecular-hybridization-conceded-exceptionally-potent-quinolinyl-oxadiazole-hybrids-through-phenyl-linked-thiosemicarbazide-antileishmanial-scaffolds-in-silico-validation-and-sar-studies
#5
Muhammad Taha, Nor Hadiani Ismail, Muhammad Ali, Umer Rashid, Syarul Imran, Nizam Uddin, Khalid Mohammed Khan
The high potential of quinoline containing natural products and their derivatives in medicinal chemistry led us to discover a novel series of compounds 6-23 based on the concept of molecular hybridization. Most of the synthesized analogues exhibited potent leishmanicidal potential. The most potent compound (23, IC50=0.10±0.001μM) among the series was found ∼70 times more lethal than the standard drug. The current series 6-23 conceded in the development of fourteen (14) extraordinarily active compounds against leishmaniasis...
February 19, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28227444/novel-3d-coaxial-flow-focusing-nozzle-device-for-the-production-of-monodispersed-collagen-microspheres
#6
Sravani Jaligama, Po-Jung Huang, Jun Kameoka, Sravani Jaligama, Po-Jung Huang, Jun Kameoka, Jun Kameoka, Sravani Jaligama, Po-Jung Huang
We have developed a 3D coaxial flow-focusing nozzle device for the mass production of monodispersed collagen microspheres and chemically crosslinked them using EDC (1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide) and N-hydroxysuccinimide (NHS). The size of the microspheres was varied between 200 μm and 600 μm by adjusting the ratio of the flow rates of the dispersed and continuous phases. MDA231-GFP cells were attached to the surface of these particles and their viability was investigated. Because they are comprised of a natural biomaterial, these collagen microspheres will have numerous applications, including bone regeneration scaffolds for tissue engineering and analyses of cancer cell interactions in a 3D environment...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28224786/cisplatin-crosslinked-multifunctional-nanodrugplexes-for-combination-therapy
#7
Weiqi Zhang, Ching-Hsuan Tung
Combination therapy efficiently tackles cancer by hitting multiple action mechanisms. However, drugs administered, simultaneously or sequentially, may not reach the targeted sites with the desired dose and ratio. The outcomes of combination therapy could be improved with a polymeric nanoparticle, which can simultaneously transport an optimal combination of drugs. We have demonstrated a simple one-pot strategy to formulate nanomedicines based on platinum coordination and the non-covalent interactions of the drugs...
February 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28224476/protein-phosphatase-2a-a-double-faced-phosphatase-of-cellular-system-and-its-role-in-neurodegenerative-disorders
#8
REVIEW
Md Nematullah, M N Hoda, Farah Khan
Protein phosphatase 2A (PP2A), a ubiquitously expressed serine/threonine phosphatase, is a vitally important phosphatase for the cellular system. Structurally, it is constituted of three different subunits, namely catalytic subunit (PP2Ac), structural scaffold subunit (PP2A-A), and regulatory subunit (PP2A-B). All subunits have various isoforms, and catalytic and scaffold subunits are ubiquitously expressed, whereas regulatory subunits are more specific to tissue and cell type. It is the numerous possibilities of PP2A holoenzyme assembly with varying isoform components that make it possess a dual nature of activator or the inhibitory character in different signaling pathways, namely neural developmental pathways, Akt/protein kinase B pathway, NF-kB pathway, MAPK pathway, apoptosis pathway, and cell cycle progression to name a few...
February 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28223689/development-of-a-new-air-stable-structure-simplified-nafuredin-%C3%AE-analog-as-a-potent-and-selective-nematode-complex-i-inhibitor
#9
Masaki Ohtawa, Shiho Arima, Risa Shimizu, Naomi Hanatani, Eri Shimizu, Kazuro Shiomi, Kiyoshi Kita, Satoshi Ōmura, Tohru Nagamitsu
Nafuredin-γ, obtained from natural nafuredin, has demonstrated a potent and selective inhibitory activity against nematode complex I. However, nafuredin-γ is unstable in air since its conjugated dienes are oxygen-labile. The instability in air was naturally solved by the synthesis of structure-simplified nafuredin-γ analogs without conjugated dienes. However, these modified analogs showed lower complex I inhibitory activities. Therefore, new air-stable structure-simplified nafuredin-γ analogs were designed and synthesized herein...
February 22, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28222891/coumarins-scaffolds-as-cox-inhibitors
#10
REVIEW
Hrishikesh Mohan Revankar, Syed Nasir Abbas Bukhari, Gajjela Bharath Kumar, Hua-Li Qin
The discovery of COX enzymes has led to a better understanding of inflammation and its related biological pathways. Apart from being related to inflammation and pain, it has also been associated with cancer and neuropsychiatric diseases such as schizophrenia. Proverbially speaking, study of these enzymes has been crucial as they happen to "have fingers in many pies". Non-steroidal anti-inflammatory drugs (NSAID) that act specifically as COX-2 inhibitors have been known for a while; however these are also associated with severe side effects such as cardiac problems...
February 9, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28221782/the-cation-%C3%AF-interaction-enables-a-halo-tag-fluorogenic-probe-for-fast-no-wash-live-cell-imaging-and-gel-free-protein-quantification
#11
Yu Liu, Kun Miao, Noah P Dunham, Hongbin Liu, Matthew Fares, Amie K Boal, Xiaosong Li, Xin Zhang
Design of fluorogenic probes for Halo-tag is highly desirable but challenging. Previous work achieved this goal by controlling the chemical switch of spirolactones upon the covalent conju-gation between Halo-tag and probes or by incorporating a 'channel dye' into the substrate bind-ing tunnel of Halo-tag. In this work, we have developed a novel class of Halo-tag fluorogenic probes that are derived from solvatochromic fluorophores. The optimal probe, harboring a ben-zothiadiazole scaffold, exhibits a 1000-fold fluorescence enhancement upon reaction with Halo-tag...
February 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/28221758/synthesis-and-fabrication-of-collagen-coated-ostholamide-electrospun-nanofiber-scaffold-for-wound-healing
#12
Subramani Kandhasamy, Sathiamurthi Perumal, Balaraman Madhan, Narayanan Umamaheswari, Javaid Ahmad Banday, Paramasivan Thirumalai Perumal, Vichangal Pridiuldi Santhanakrishnan
A novel scaffold for effective wound healing treatment was developed utilizing natural product bearing collagen based biocompatible electro-spun nanofibres. Initially, ostholamide (OSA) was synthesized from osthole (a natural coumarin), characterized by 1H, 13C, DEPT-135 NMR, ESI-MS and FT-IR spectroscopy analysis. OSA was incorporated into Polyhydroxybutyrate (PHB) and Gelatin (GEL), which serve as templates for electro-spun nanofibers. The coating of OSA-PHB-GEL nanofibers with collagen resulted in PHB-GEL-OSA-COL nanofibrous scaffold which mimics extra cellular matrix and serves as an effective biomaterial for tissue engineering applications, especially for wound healing...
February 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28221346/synthesis-of-ent-be-43547a1-reveals-a-potent-hypoxia-selective-anticancer-agent-and-uncovers-the-biosynthetic-origin-of-the-apd-cld-natural-products
#13
Nikolaj L Villadsen, Kristian M Jacobsen, Ulrik B Keiding, Esben T Weibel, Bjørn Christiansen, Thomas Vosegaard, Morten Bjerring, Frank Jensen, Mogens Johannsen, Thomas Tørring, Thomas B Poulsen
Tumour hypoxia is speculated to be a key driver of therapeutic resistance and metastatic dissemination. Consequently, the discovery of new potent agents that selectively target the hypoxic cell population may reveal new and untapped antitumour mechanisms. Here we demonstrate that the BE-43547 subclass of the APD-CLD (amidopentadienoate-containing cyclolipodepsipeptides) natural products possesses highly hypoxia-selective growth-inhibitory activity against pancreatic cancer cells. To enable this discovery, we have developed the first synthesis of the BE-43547-macrocyclic scaffold in 16 steps (longest linear sequence), which also allowed access to the full panel of relative stereoisomers and ultimately to the assignment of stereochemical configuration...
March 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28221007/ionic-colloidal-molding-as-a-biomimetic-scaffolding-strategy-for-uniform-bone-tissue-regeneration
#14
Jian Zhang, Jinpeng Jia, Jimin P Kim, Hong Shen, Fei Yang, Qiang Zhang, Meng Xu, Wenzhi Bi, Xing Wang, Jian Yang, Decheng Wu
Inspired by the highly ordered nanostructure of bone, nanodopant composite biomaterials are gaining special attention for their ability to guide bone tissue regeneration through structural and biological cues. However, bone malformation in orthopedic surgery is a lingering issue, partly due to the high surface energy of traditional nanoparticles contributing to aggregation and inhomogeneity. Recently, carboxyl-functionalized synthetic polymers have been shown to mimic the carboxyl-rich surface motifs of non-collagenous proteins in stabilizing hydroxyapatite and directing intrafibrillar mineralization in-vitro...
February 21, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28220885/cancer-cell-mitochondria-targeting-by-pancratistatin-analogs-is-dependent-on-functional-complex-ii-and-iii
#15
Dennis Ma, Christopher Pignanelli, Daniel Tarade, Tyler Gilbert, Megan Noel, Fadi Mansour, Scott Adams, Alexander Dowhayko, Kyle Stokes, Sergey Vshyvenko, Tomas Hudlicky, James McNulty, Siyaram Pandey
Enhanced mitochondrial stability and decreased dependence on oxidative phosphorylation confer an acquired resistance to apoptosis in cancer cells, but may present opportunities for therapeutic intervention. The compound pancratistatin (PST) has been shown to selectively induce apoptosis in cancer cells. However, its low availability in nature has hindered its clinical advancement. We synthesized PST analogs and a medium-throughput screen was completed. Analogs SVTH-7, -6, and -5 demonstrated potent anti-cancer activity greater than PST and several standard chemotherapeutics...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220535/interaction-of-approved-drugs-with-synaptic-vesicle-protein-2a
#16
Azeem Danish, Vigneshwaran Namasivayam, Anke C Schiedel, Christa E Müller
Levetiracetam (LEV) and its recently approved derivative brivaracetam are anti-epileptic drugs with a unique mechanism of action. The synaptic vesicle protein 2A (SV2A) was previously identified as their main target. In the current study, we tested a collection of 500 approved drugs for interaction with the human SV2A protein expressed in Chinese hamster ovary cells. Competition binding studies were performed using cell lysates with high SV2A expression and [(3) H]brivaracetam as a radioligand. A hit rate of 3% was obtained, defined as compounds that inhibited radioligand binding by more than 90% at a screening concentration of 20 μM...
February 21, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28219742/the-use-of-nanoscaffolds-and-dendrimers-in-tissue-engineering
#17
REVIEW
Bapi Gorain, Muktika Tekade, Prashant Kesharwani, Arun K Iyer, Kiran Kalia, Rakesh Kumar Tekade
To avoid tissue rejection during organ transplantation, research has focused on the use of tissue engineering to regenerate required tissues or organs for patients. The biomedical applications of hyperbranched, multivalent, structurally uniform, biocompatible dendrimers in tissue engineering include the mimicking of natural extracellular matrices (ECMs) in the 3D microenvironment. Dendrimers are unimolecular architects that can incorporate a variety of biological and/or chemical substances in a 3D architecture to actively support the scaffold microenvironment during cell growth...
February 20, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28218301/cuttlebone-like-v2o5-nanofibre-scaffolds-advances-in-structuring-cellular-solids
#18
Andrea Knöller, Tomče Runčevski, Robert E Dinnebier, Joachim Bill, Zaklina Burghard
The synthesis of ceramic materials combining high porosity and permeability with good mechanical stability is challenging, as optimising the latter requires compromises regarding the first two properties. Nonetheless, significant progress can be made in this direction by taking advantage of the structural design principles evolved by nature. Natural cellular solids achieve good mechanical stability via a defined hierarchical organisation of the building blocks they are composed of. Here, we report the first synthetic, ceramic-based scaffold whose architecture closely mimics that of cuttlebone -a structural biomaterial whose porosity exceeds that of most other natural cellular solids, whilst preserving an excellent mechanical strength...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28217993/assessment-of-label-free-quantification-in-discovery-proteomics-and-impact-of-technological-factors-and-natural-variability-of-protein-abundance
#19
Mhd Rami Al Shweiki, Susann Mönchgesang, Petra Majovsky, Domenika Thieme, Diana Trutschel, Wolfgang Hoehenwarter
We evaluated the state of label-free discovery proteomics focusing especially on technological contributions and contributions of naturally occurring differences in protein abundance to the inter-sample variability in protein abundance estimates in this highly peptide-centric technology. First, the performance of popular quantitative proteomics software, Proteome Discoverer, Scaffold, MaxQuant and Progenesis QIP was benchmarked using their default parameters and some modified settings. Beyond this the inter- sample variability in protein abundance estimates was decomposed into variability introduced by the entire technology itself and variable protein amounts inherent to individual plants of the Arabidopsis thaliana Col-0 accession...
February 20, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28216298/cell-instructive-starpeg-heparin-collagen-composite-matrices
#20
Marcus Binner, Laura J Bray, Jens Friedrichs, Uwe Freudenberg, Mikhail V Tsurkan, Carsten Werner
: Polymer hydrogels can be readily modulated with regard to their physical properties and functionalized to recapitulate molecular cues of the extracellular matrix (ECM). However, they remain structurally different from the hierarchical supramolecular assemblies of natural ECM. Accordingly, we herein report a set of hydrogel composite materials made from starPEG-peptide conjugates, maleimide-functionalized heparin and collagen type I that combine semisynthetic and ECM-derived components...
February 16, 2017: Acta Biomaterialia
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