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https://www.readbyqxmd.com/read/29334370/scaffolds-that-mimic-antigen-presenting-cells-enable-ex-vivo-expansion-of-primary-t-cells
#1
Alexander S Cheung, David K Y Zhang, Sandeep T Koshy, David J Mooney
Therapeutic ex vivo T-cell expansion is limited by low rates and T-cell products of limited functionality. Here we describe a system that mimics natural antigen-presenting cells (APCs) and consists of a fluid lipid bilayer supported by mesoporous silica micro-rods. The lipid bilayer presents membrane-bound cues for T-cell receptor stimulation and costimulation, while the micro-rods enable sustained release of soluble paracrine cues. Using anti-CD3, anti-CD28, and interleukin-2, we show that the APC-mimetic scaffolds (APC-ms) promote two- to tenfold greater polyclonal expansion of primary mouse and human T cells compared with commercial expansion beads (Dynabeads)...
January 15, 2018: Nature Biotechnology
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
#2
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/29333088/bone-regeneration-using-silk-hydroxyapatite-hybrid-composite-in-a-rat-alveolar-defect-model
#3
Kyung S Koh, Jong Woo Choi, Eun Jeong Park, Tae Suk Oh
Background: To overcome the limited source of autogenous bone in bone grafting, many efforts have been made to find bone substitutes. The use of hybrid composites of silk and hydroxyapatite to simulate natural bone tissue can overcome the softness and brittleness of the individual components. Methods: Critical-sized, 7 x 4 x 1.5 mm alveolar defects were created surgically in 36 Sprague-Dawley rats. Three treatment groups were tested: an empty defect group (group I), a silk fibrin scaffold group (group II), and a hydroxyapatite-conjugated silk fibrin scaffold group (group III)...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29332574/biomacromolecular-based-fibers-in-nanomedicine-a-combination-of-drug-delivery-and-tissue-engineering
#4
Elham Arkan, Abbas Hemati Azandaryani, Pouran Moradipour, Leila Behbood
BACKGROUND: Biopolymers based materials (polysaccharides, lipids, proteins, and nucleic acids) are one of the basic resources in bio-engineering sciences because of desirable features. Moreover, nanobiotechnology innovates nanomaterial and associated technique in nano medicine (drug delivery and tissue engineering). METHODS: In the nano-medicine, fibers are introduced as a successful biomimetic extracellular matrix scaffolds and drug carrier systems. Electrospinning as a simple and cost-effective technique is used to design nanofibers...
January 12, 2018: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29332052/when-art-meets-gardens-does-it-enhance-the-benefits-the-nancy-hypothesis-of-care-for-persons-with-alzheimer-s-disease
#5
Thérèse Rivasseau Jonveaux, Reinhard Fescharek
The creation of healing gardens for persons with Alzheimer's disease and related diseases (ADRD) offers vast potential. They can play a role in the scaffolding of cognitive disorders, emotional stress, sensory processing, sense of harmony, and appeasement. These effects are achieved through a distributed interplay of psychological functions with the immediate environment and local culture on the one hand, and dialogue on the other. The garden, a natural canvas created by man, shares with art the ability to foster an esthetic sense for which the perception can be measured by functional neurological imaging exploration...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29331223/structure-based-design-and-application-of-a-nucleotide-coenzyme-mimetic-ligand-application-to-the-affinity-purification-of-nucleotide-dependent-enzymes
#6
Marigianna Marinou, Dimitrios Platis, Farid S Ataya, Evangelia Chronopoulou, Dimitrios Vlachakis, Nikolaos E Labrou
In the present study, a structure-based approach was exploited for the in silico design of a nucleotide coenzyme mimetic ligand. The enzyme formate dehydrogenase (FDH) was employed as a model in our study. The biomimetic ligand was designed and synthesized based on a tryptamine/3-aminopropylphosphonic acid bi-substituted 1,3,5-triazine (Trz) scaffold (Tra-Trz-3APP), which potentially mimics the interactions of NAD+-FDH complex. Molecular docking studies of the biomimetic ligand predicted that it can occupy the same binding site as the natural coenzyme...
January 3, 2018: Journal of Chromatography. A
https://www.readbyqxmd.com/read/29328655/identification-of-novel-coumestan-derivatives-as-polyketide-synthase-13-inhibitors-against-mycobacterium-tuberculosis
#7
Wei Zhang, Shichun Lun, Shu-Huan Wang, Xingwu Jiang, Fan Yang, Jie Tang, Abigail L Manson, Ashlee M Earl, Hendra Gunosewoyo, William R Bishai, Li-Fang Yu
Inhibition of the mycolic acid pathway has proven a viable strategy in antitubercular drug discovery. The AccA3/AccD4/FadD32/Pks13 complex of Mycobacterium tuberculosis constitutes an essential biosynthetic mechanism for mycolic acids. Small molecules targeting the thioesterase domain of Pks13 have been reported, including a benzofuran-based compound, whose X-ray co-crystal structure has been very recently solved. Its initial inactivity in a serum inhibition titration (SIT) assay led us to further probe other structurally-related benzofurans with the aim to improve their potency and bioavailability...
January 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29327718/epithelioid-fibrous-histiocytoma-molecular-characterization-of-alk-fusion-partners-in-23-cases
#8
Brendan C Dickson, David Swanson, George S Charames, Christopher Dm Fletcher, Jason L Hornick
Epithelioid fibrous histiocytoma is a rare and distinctive cutaneous neoplasm. Most cases harbor ALK rearrangement and show ALK overexpression, which distinguish this neoplasm from conventional cutaneous fibrous histiocytoma and variants. SQSTM1 and VCL have previously been shown to partner with ALK in one case each of epithelioid fibrous histiocytoma. The purpose of this study was to examine a large cohort of epithelioid fibrous histiocytomas by next-generation sequencing to characterize the nature and prevalence of ALK fusion partners...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29326018/semisynthesis-cytotoxicity-antimalarial-evaluation-and-structure-activity-relationship-of-two-series-of-triterpene-derivatives
#9
Simone Tasca Cargnin, Andressa Finkler Staudt, Patrícia Medeiros, Daniel de Medeiros Sol Sol, Ana Paula de Azevedo Dos Santos, Fernando Berton Zanchi, Grace Gosmann, Antonio Puyet, Carolina Bioni Garcia Teles, Simone Baggio Gnoatto
In this report, we describe the semisynthesis of two series of ursolic and betulinic acid derivatives through designed by modifications at the C-3 and C-28 positions and demonstrate their antimalarial activity against chloroquine-resistant P. falciparum (W2 strain). Structural modifications at C-3 were more advantageous to antimalarial activity than simultaneous modifications at C-3 and C-28 positions. The ester derivative, 3β-butanoyl betulinic acid (7b), was the most active compound (IC50 = 3.4 µM) and it did not exhibit cytotoxicity against VERO nor HepG2 cells (CC50 > 400 µM), showing selectivity towards parasites (selectivity index > 117...
December 29, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29324067/mao-inhibitors-and-their-wider-applications-a-patent-review
#10
Simone Carradori, Daniela Secci, Jacques P Petzer
Monoamine oxidase (MAO) inhibitors, after the initial "golden age", are currently used as third-line antidepressants (selective MAO-A inhibitors) or clinically enrolled as co-adjuvants for neurodegenerative diseases (selective MAO-B inhibitors). However, the research within this field is always increasing due to their pivotal role in modulating synaptic functions and monoamines metabolism. Areas covered: In this paper, MAO inhibitors (2015-2017) are disclosed ordering all the patents according to their chemical scaffold...
January 11, 2018: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29320372/a-dentin-derived-hydrogel-bioink-for-3d-bioprinting-of-cell-laden-scaffolds-for-regenerative-dentistry
#11
Avathamsa Athirasala, Anthony Tahayeri, Greeshma Thrivikraman, Cristiane M França, Nelson Monteiro, Victor Tran, Jack Ferracane, Luiz E Bertassoni
Recent studies in tissue engineering have adopted extracellular matrix (ECM) derived scaffolds as natural and cytocompatible microenvironments for tissue regeneration. The dentin matrix, specifically, has been shown to be associated with a host of soluble and insoluble signaling molecules that can promote odontogenesis. Here, we have developed a novel bioink, blending printable alginate (3% w/v) hydrogels with the soluble and insoluble fractions of the dentin matrix. We have optimized the printing parameters and the concentrations of the individual components of the bioink for print accuracy, cell viability and odontogenic potential...
January 10, 2018: Biofabrication
https://www.readbyqxmd.com/read/29318958/a-cell-engineered-small-intestinal-submucosa-based-bone-mimetic-construct-for-bone-regeneration
#12
Mei Li, Chi Zhang, Yuxing Mao, Yi Zhong, Jiyuan Zhao
Extracellular matrix (ECM)-ornamented biomaterials have attracted attention due to their high potential to improve the bio-functionality of original materials. It is thought that ECM with a bone mimetic microenvironment generated by the specific induction of osteoblasts would be more beneficial for bone regeneration than regular ECM. In this study, we developed an osteogenic and mineralized ECM construct (Os/M-ECM-SIS) under the guidance of osteoblasts on a small intestinal submucosa (SIS) scaffold co-treated with icariin and calcium...
January 10, 2018: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29317369/mesenchymal-stem-cell-derived-extracellular-matrix-enhances-chondrogenic-phenotype-of-and-cartilage-formation-by-encapsulated-chondrocytes-in-vitro-and-in-vivo
#13
Yuanheng Yang, Hang Lin, He Shen, Bing Wang, Guanghua Lei, Rocky S Tuan
Mesenchymal stem cell derived extracellular matrix (MSC-ECM) is a natural biomaterial with robust bioactivity and good biocompatibility, and has been studied as a scaffold for tissue engineering. In this investigation, we tested the applicability of using decellularized human bone marrow derived MSC-ECM (hBMSC-ECM) as a culture substrate for chondrocyte expansion in vitro, as well as a scaffold for chondrocyte-based cartilage repair. hBMSC-ECM deposited by hBMSCs cultured on tissue culture plastic (TCP) was harvested, and then subjected to a decellularization process to remove hBMSCs...
January 6, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29314593/in-vivo-immuno-reactivity-analysis-of-the-porous-3d-cs-sio2-and-cs-sio2-ha-hybrids
#14
Mengxia Guo, Yifan Dong, Jiangwei Xiao, Ruicai Gu, Maochao Ding, Tao Huang, Junhua Li, Naru Zhao, Hua Liao
Inorganic/organic hybrid silica-chitosan scaffolds have promising potential for bone defect repair, due to the controllable mechanical properties, degradation behavior and scaffold morphology. However, the precise in vivo immuno-reactivity of silica-chitosan hybrids with various compositions is still poorly defined. In this study, we fabricated the 3D interconnected porous chitosan-silica (CS/SiO2 ) and chitosan-silica-hydroxyapatite (CS/SiO2 /HA) hybrids, through sol-gel process and 3D plotting skill, followed by the naturally or freeze drying separately...
January 3, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29313681/the-cyanthiwigin-natural-product-core-as-a-complex-molecular-scaffold-for-comparative-late-stage-c-h-functionalization-studies
#15
Kelly E Kim, Ashley M Adams, Nicholas D Chiappini, J Du Bois, Brian M Stoltz
The desire for maximally efficient transformations in complex molecule synthesis has contributed to a surge of interest in C-H functionalization methods development in recent years. In contrast to the steady stream of methodological reports, however, there are noticeably fewer studies comparing the efficacies of different C-H functionalization protocols on a single structurally intricate substrate. Recognizing the importance of heteroatom incorporation in complex molecule synthesis, this report discloses a comparative examination of diverse strategies for C-O, C-N, and C-X bond formation through late-stage C-H oxidation of the tricyclic cyanthiwigin natural product core...
January 9, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29313189/supportive-properties-of-basement-membrane-layer-of-human-amniotic-membrane-enable-development-of-tissue-engineering-applications
#16
Sonia Iranpour, Nasser Mahdavi-Shahri, Raheleh Miri, Halimeh Hasanzadeh, Hamid Reza Bidkhori, Hojjat Naderi-Meshkin, Ehsan Zahabi, Maryam M Matin
Human amniotic membrane (HAM) has been widely used as a natural scaffold in tissue engineering due to many of its unique biological properties such as providing growth factors, cytokines and tissue inhibitors of metalloproteinases. This study aimed at finding the most suitable and supportive layer of HAM as a delivery system for autologous or allogeneic cell transplantation. Three different layers of HAM were examined including basement membrane, epithelial and stromal layers. In order to prepare the basement membrane, de-epithelialization was performed using 0...
January 8, 2018: Cell and Tissue Banking
https://www.readbyqxmd.com/read/29311466/-elaboration-of-pseudo-natural-products-using-artificial-in-vitro-biosynthesis-systems
#17
Yuki Goto
 Peptidic natural products often consist of not only proteinogenic building blocks but also unique non-proteinogenic structures such as macrocyclic scaffolds and N-methylated backbones. Since such non-proteinogenic structures are important structural motifs that contribute to diverse bioactivity, we have proposed that peptides with non-proteinogenic structures should be attractive candidates as artificial bioactive peptides mimicking natural products, or so-called pseudo-natural products. We previously devised an engineered translation system for pseudo-natural peptides, referred to as the flexible in vitro translation (FIT) system...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/29306082/effect-of-freezing-conditions-on-%C3%AE-tricalcium-phosphate-camphene-scaffold-with-micro-sized-particles-fabricated-by-freeze-casting
#18
Gurdev Singh, S Soundarapandian
The long standing need of the implant manufacturing industries is to fabricate multi-matrix, customized porous scaffold as cost-effectively. In recent years, freeze casting has shown greater opportunity in the fabrication of porous scaffolds (tricalcium phosphate, hydroxyapatite, bioglass, alumina, etc.) such as at ease and good control over pore size, porosity, a range of materials and economic feasibility. In particular, tricalcium phosphate (TCP) has proved as it possesses good biocompatible (osteoinduction, osteoconduction, etc...
December 30, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/29305695/production-of-%C3%AE-keto-carboxylic-acid-dimers-in-yeast-by-overexpression-of-nrps-like-genes-from-aspergillus-terreus
#19
Elisabeth Hühner, Katja Backhaus, Rixa Kraut, Shu-Ming Li
Non-ribosomal peptide synthetases (NRPSs) are key enzymes in microorganisms for the assembly of peptide backbones of biologically and pharmacologically active natural products. The monomodular NRPS-like enzymes comprise often an adenylation (A), a thiolation (T), and a thioesterase (TE) domain. In contrast to the NRPSs, they do not contain any condensation domain and usually catalyze a dimerization of α-keto carboxylic acids and thereby provide diverse scaffolds for further modifications. In this study, we established an expression system for NRPS-like genes in Saccharomyces cerevisiae...
January 5, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29303201/inexpensive-multigram-scale-synthesis-of-cyclic-enamines-and-3-n-spirocyclopropyl-systems
#20
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
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