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https://www.readbyqxmd.com/read/28343149/%C3%AE-adrenergic-stimulation-induces-histone-deacetylase-5-hdac5-nuclear-accumulation-in-cardiomyocytes-by-b55%C3%AE-pp2a-mediated-dephosphorylation
#1
Kate L Weeks, Antonella Ranieri, Agnieszka Karaś, Bianca C Bernardo, Alexandra S Ashcroft, Chris Molenaar, Julie R McMullen, Metin Avkiran
BACKGROUND: Class IIa histone deacetylase (HDAC) isoforms such as HDAC5 are critical signal-responsive repressors of maladaptive cardiomyocyte hypertrophy, through nuclear interactions with transcription factors including myocyte enhancer factor-2. β-Adrenoceptor (β-AR) stimulation, a signal of fundamental importance in regulating cardiac function, has been proposed to induce both phosphorylation-independent nuclear export and phosphorylation-dependent nuclear accumulation of cardiomyocyte HDAC5...
March 25, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28343003/essential-design-considerations-for-the-resazurin-reduction-assay-to-noninvasively-quantify-cell-expansion-within-perfused-extracellular-matrix-scaffolds
#2
Joseph S Uzarski, Michael D DiVito, Jason A Wertheim, William M Miller
Precise measurement of cellularity within bioartificial tissues and extracellular matrix (ECM) scaffolds is necessary to augment rigorous characterization of cellular behavior, as accurate benchmarking of tissue function to cell number allows for comparison of data across experiments and between laboratories. Resazurin, a soluble dye that is reduced to highly fluorescent resorufin in proportion to the metabolic activity of a cell population, is a valuable, noninvasive tool to measure cell number. We investigated experimental conditions in which resazurin reduction is a reliable indicator of cellularity within three-dimensional (3D) ECM scaffolds...
February 16, 2017: Biomaterials
https://www.readbyqxmd.com/read/28342939/recent-synthetic-and-medicinal-perspectives-of-dihydropyrimidinones-a-review
#3
REVIEW
Ramandeep Kaur, Sandeep Chaudhary, Kapil Kumar, Manish K Gupta, Ravindra K Rawal
Dihydropyrimidines are the most important heterocyclic ring systems which play an important role in the synthesis of DNA and RNA. Synthetically they were synthesized using Multi-component reactions like Biginelli reaction and Hantzschdihydropyridine. In the past decades, such Biginelli type dihydropyrimidones have received a considerable amount of attention due to the interesting pharmacological properties associated with this heterocyclic scaffold. In this review, we highlight recent developments in this area, with a focus on the DHPMs, recently developed as anti-inflammatory, anti-HIV, anti-tubercular, antifungal anticancer, antibacterial, antifilarial, antihyperglycemic, antihypertensive, analgesic, anti-convulsant, antioxidant, anti-TRPA1, anti-SARS, and anti-cancer activity and α1a binding affinity...
March 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28342879/stable-subcutaneous-cartilage-regeneration-of-bone-marrow-stromal-cells-directed-by-chondrocyte-sheet
#4
Dan Li, Lian Zhu, Yu Liu, Zongqi Yin, Yi Liu, Fangjun Liu, Aijuan He, Shaoqing Feng, Yixin Zhang, Zhiyong Zhang, Wenjie Zhang, Wei Liu, Yilin Cao, Guangdong Zhou
In vivo niche plays an important role in regulating differentiation fate of stem cells. Due to lack of proper chondrogenic niche, stable cartilage regeneration of bone marrow stromal cells (BMSCs) in subcutaneous environments is always a great challenge. This study explored the feasibility that chondrocyte sheet created chondrogenic niche retained chondrogenic phenotype of BMSC engineered cartilage (BEC) in subcutaneous environments. Porcine BMSCs were seeded into biodegradable scaffolds followed by 4 weeks of chondrogenic induction in vitro to form BEC, which were wrapped with chondrocyte sheets (Sheet group), acellular small intestinal submucosa (SIS, SIS group), or nothing (Blank group) respectively and then implanted subcutaneously into nude mice to trace the maintenance of chondrogenic phenotype...
March 22, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28342878/3d-printing-for-the-design-and-fabrication-of-polymer-based-gradient-scaffolds
#5
Laura G Bracaglia, Brandon T Smith, Emma Watson, Navein Arumugasaamy, Antonios G Mikos, John P Fisher
To accurately mimic the native tissue environment, tissue engineered scaffolds often need to have a highly controlled and varied display of three-dimensional (3D) architecture and geometrical cues. Additive manufacturing in tissue engineering has made possible the development of complex scaffolds that mimic the native tissue architectures. As such, architectural details that were previously unattainable or irreproducible can now be incorporated in an ordered and organized approach, further advancing the structural and chemical cues delivered to cells interacting with the scaffold...
March 22, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28342744/synthesis-and-anti-cancer-activity-of-chiral-tetrahydropyrazolo-1-5-a-pyridine-fused-steroids
#6
Susana M M Lopes, Emanuel P Sousa, Luísa Barreira, Cátia Marques, Maria João Rodrigues, Teresa M V D Pinho E Melo
Regio- and stereoselective synthesis of novel chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused steroids via [8π+2π] cycloaddition of diazafulvenium methides with steroidal scaffolds is reported. The biological evaluation of the new family of hexacyclic steroids as anti-cancer agents was also carried out. Hexacyclic steroids bearing a benzyl group at C-22, derived from 16-dehydropregnenolone and 16-dehydroprogesterone, show considerable cytotoxicity against EL4 (murine T-lymphoma) in contrast with the corresponding C-22-unsubstituted derivatives showing low cytotoxicity...
March 22, 2017: Steroids
https://www.readbyqxmd.com/read/28342691/indenocinnoline-derivatives-as-g-quadruplex-binders-topoisomerase-ii%C3%AE-inhibitors-and-antiproliferative-agents
#7
Grigoris Zoidis, Alice Sosic, Silvia Da Ros, Barbara Gatto, Claudia Sissi, Fausta Palluotto, Angelo Carotti, Marco Catto
DNA intercalating agents are a consolidated therapeutic option in the treatment of tumor diseases. Starting from previous findings in the antiproliferative efficacy of a series of indeno[1,2-c]cinnoline-11-one derivatives, we performed a suitable decoration of this scaffold by means of a simple and straightforward chemistry, aiming to a) enlarge the planar core to a pentacyclic benzo[h]indeno[1,2-c]cinnoline-13-one and b) introduce a basic head tethered through a simple polymethylene chain. In fluorescence melting and fluorescence intercalator displacement assays, these new compounds displayed fair to very good intercalating properties on different nucleic acid strands, with preference for G-quadruplex sequences...
March 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28342366/discovery-of-new-dual-ppar%C3%AE-gpr40-agonists-with-robust-antidiabetic-activity-design-synthesis-and-in-combo-drug-evaluation
#8
Sergio Hidalgo-Figueroa, Gabriel Navarrete-Vázquez, Samuel Estrada-Soto, Diana Giles-Rivas, Francisco J Alarcón-Aguilar, Ismael León-Rivera, Abraham Giacoman-Martínez, Elizabeth Miranda Pérez, Julio C Almanza-Pérez
The design of compounds 1 and 2 was based on the similar scaffold of pharmacophoric groups for PPARγ and GPR40 agonists. In order to find new compounds with improved biological activity, the current manuscript describes a new dual PPARγ-GPR40 agonist. We synthesized two compounds, which were prepared following a multistep synthetic route, and the relative mRNA expression levels of PPARγ, GLUT4, and GPR40 were quantified in cell culture, as well as insulin secretion and [Ca(2+)] intracellular levels. Compound 1 showed a 7-times increase in the mRNA expression of PPARγ, which in turn enhanced the expression levels of GLUT4 respect to control and pioglitazone...
March 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28342325/development-of-a-rapid-matrix-digestion-technique-for-ultrastructural-analysis-of-elastic-fibers-in-the-intervertebral-disc
#9
Javad Tavakoli, John J Costi
Collagen and elastic fibers are two major fibrous constituents of the annulus fibrosus (AF) in the disc that contribute to its mechanical and viscoelastic properties. It was thought that elastic fibers play no substantial role in the function and properties of the disc as these fibers were irregularly distributed. Studies that have revealed highly organized elastic fibers with different regional orientation and distribution, while being strongly crosslinked with matrix, suggesting their contribution to disc structure-function properties...
March 21, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28342324/short-bursts-of-cyclic-mechanical-compression-modulate-tissue-formation-in-a-3d-hybrid-scaffold
#10
M Brunelli, C M Perrault, D Lacroix
Among the cues affecting cells behaviour, mechanical stimuli are known to have a key role in tissue formation and mineralization of bone cells. While soft scaffolds are better at mimicking the extracellular environment, they cannot withstand the high loads required to be efficient substitutes for bone in vivo. We propose a 3D hybrid scaffold combining the load-bearing capabilities of polycaprolactone (PCL) and the ECM-like chemistry of collagen gel to support the dynamic mechanical differentiation of human embryonic mesodermal progenitor cells (hES-MPs)...
March 18, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28340368/synthesis-molecular-docking-antimycobacterial-and-antimicrobial-evaluation-of-new-pyrrolo-3-2-c-pyridine-mannich-bases
#11
Gilish Jose, Tholappanavara H Suresha Kumara, Haliwana B V Sowmya, Dharmarajan Sriram, Tayur N Guru Row, Amar A Hosamani, Sunil S More, Bhavya Janardhan, B G Harish, Sandeep Telkar, Yalegara Siddappa Ravikumar
In this report, we describe the synthesis and biological evaluation of a new series of pyrrolo[3,2-c]pyridine Mannich bases (7a-v). The Mannich bases were obtained in good yields by one-pot three component condensation of pyrrolo[3,2-c]pyridine scaffold (6a-c) with secondary amines and excess of formaldehyde solution in AcOH. The chemical structures of the compounds were characterized by (1)H NMR, (13)C NMR, LC/MS and elemental analysis. Single crystal X-ray diffraction has been recorded for compound 7k ([C23H29ClN4](+2), H2O)...
March 16, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28340294/a-well-defined-osmium-cupin-complex-hyperstable-artificial-osmium-peroxygenase
#12
Nobutaka Fujieda, Takumi Nakano, Yuki Taniguchi, Haruna Ichihashi, Hideki Sugimoto, Yuma Morimoto, Yosuke Nishikawa, Genji Kurisu, Shinobu Itoh
Thermally stable TM1459 cupin superfamily protein from Thermotoga maritima was repurposed as an osmium (Os) peroxygenase by metal-substitution strategy employing the metal-binding promiscuity. This novel artificial metalloenzyme bears a datively bound Os ion supported by the 4-histidine motif. The well-defined Os center is responsible for not only the catalytic activity but also the thermodynamic stability of the protein folding, leading to the robust biocatalyst (Tm ≈ 120 °C). The spectroscopic analysis and atomic resolution X-ray crystal structures of Os-bound TM1459 revealed two types of donor sets to Os center with octahedral coordination geometry...
March 24, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28339553/de-and-recellularization-of-the-pig-uterus-a-bioengineering-pilot-study%C3%A2
#13
Hannes Campo, Pedro M Baptista, Nuria López-Pérez, Amparo Faus, Irene Cervelló, Carlos Simón
Absolute uterine factor infertility, or the absence of a functional uterus, has a prevalence of 3%-5% in the general population. Despite the great strides being made in reproductive medicine, patients diagnosed with absolute uterine factor infertility remain untreatable. The only available solution has been gestational surrogacy, but recently the Brannström group presented a viable alternative by reporting the first successful live birth after uterus transplantation. Similar to other transplantations, this approach has inherent limitations such as the paucity of donor organs and the need for long-term immunosuppression...
December 27, 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/28339213/quaternary-carbon-center-forming-formal-3-3-cycloaddition-reaction-via-bifunctional-catalysis-asymmetric-synthesis-of-spirocyclohexene-pyrazolones
#14
Jin-Yu Liu, Jing Zhao, Jia-Lu Zhang, Peng-Fei Xu
A variety of spirocyclohexene pyrazolones were synthesized in good yields with excellent stereoselectivities through an asymmetric, intermolecular, quaternary carbon center forming [3 + 3] cycloaddition reaction catalyzed by a bifunctional catalyst. The vinylogous pyrazolones used as binucleophilic synthons in this reaction exhibited superior ability for constructing pyrazolone related spirocyclic scaffolds.
March 24, 2017: Organic Letters
https://www.readbyqxmd.com/read/28339186/quantum-chemical-strain-analysis-for-mechanochemical-processes
#15
Tim Stauch, Andreas Dreuw
The use of mechanical force to initiate a chemical reaction is an efficient alternative to the conventional sources of activation energy, i.e., heat, light, and electricity. Applications of mechanochemistry in academic and industrial laboratories are diverse, ranging from chemical syntheses in ball mills and ultrasound baths to direct activation of covalent bonds using an atomic force microscope. The vectorial nature of force is advantageous because specific covalent bonds can be preconditioned for rupture by selective stretching...
March 24, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28338687/remote-c-h-alkylation-and-c-c-bond-cleavage-enabled-by-an-in-situ-generated-palladacycle
#16
Juntao Ye, Zhihao Shi, Theresa Sperger, Yoshifumi Yasukawa, Cian Kingston, Franziska Schoenebeck, Mark Lautens
The direct and selective functionalization of C-H bonds of arenes is one of the most challenging yet valuable aims in organic synthesis. Despite notable recent achievements, a pre-installed directing group proved to be essential in most of the methodologies reported so far. In this context, the use of a transient directing group that can be generated in situ has attracted attention and demonstrated the great potential of this strategy. Here we report the use of an in situ generated palladacycle to accomplish remote-selective C-H alkylation reactions of arenes...
April 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28338623/a-study-of-intramolecular-hydrogen-bonding-in-levoglucosan-derivatives
#17
Lucas Quiquempoix, Elena Bogdan, Neil J Wells, Jean-Yves Le Questel, Jérôme Graton, Bruno Linclau
Organofluorine is a weak hydrogen-bond (HB) acceptor. Bernet et al. have demonstrated its capability to perturb OH···O intramolecular hydrogen bonds (IMHBs), using conformationally rigid carbohydrate scaffolds including levoglucosan derivatives. These investigations are supplemented here by experimental and theoretical studies involving six new levoglucosan derivatives, and complement the findings of Bernet et al. However, it is shown that conformational analysis is instrumental in interpreting the experimental data, due to the occurrence of non-intramolecular hydrogen-bonded populations which, although minor, cannot be neglected and appears surprisingly significant...
March 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28338602/design-and-synthesis-of-novel-pyrazole-substituted-different-nitrogenous-heterocyclic-ring-systems-as-potential-anti-inflammatory-agents
#18
Eman S Nossier, Hoda H Fahmy, Nagy M Khalifa, Wafaa I El-Eraky, Marawan A Baset
With the aim of developing novel anti-inflammatory scaffolds, a new series of pyrazole-substituted various nitrogenous heterocyclic ring systems at C-4 position were synthesized through different chemical reactions and validated by means of spectral and elemental data. The new obtained compounds were investigated for their anti-inflammatory activity using the carrageenan-induced paw edema standard technique and revealed that, compound 6b showed increased potency with % inhibition of edema 85.23 ± 1.92 and 85...
March 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28338421/harnessing-the-osteogenicity-of-in-vitro-stem-cell-derived-mineralized-extracellular-matrix-as-3d-biotemplate-to-guide-bone-regeneration
#19
Yoke Chin Chai, Johanna Bolander, Ioannis Papantoniou, Jennifer Patterson, Jef Vleugels, Jan Schrooten, Frank P Luyten
Advanced biomaterials that are capable of guiding robust bone regeneration are highly demanded for translational therapy of bone defects or bone augmentation in clinics. One of the strategic approaches is to produce tissue engineering (TE) constructs that mediate bone regeneration by recapitulating the natural bone formation or healing process. In this study, we aimed at producing devitalized mineralized carriers with augmented bone forming capacity via a modified culture protocol (i.e., culture conditions with high calcium and/or phosphate concentrations) that first promotes cell growth and, subsequently, mineralized extracellular matrix (ECM) deposition by human periosteum-derived osteoprogenitor cells (hPDCs) on additive manufactured three-dimensional (3D) porous titanium (Ti)-based scaffolds...
March 24, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28338091/intermediate-filament-reorganization-dynamically-influences-cancer-cell-alignment-and-migration
#20
Andrew W Holle, Melih Kalafat, Adria Sales Ramos, Thomas Seufferlein, Ralf Kemkemer, Joachim P Spatz
The interactions between a cancer cell and its extracellular matrix (ECM) have been the focus of an increasing amount of investigation. The role of the intermediate filament keratin in cancer has also been coming into focus of late, but more research is needed to understand how this piece fits in the puzzle of cytoskeleton-mediated invasion and metastasis. In Panc-1 invasive pancreatic cancer cells, keratin phosphorylation in conjunction with actin inhibition was found to be sufficient to reduce cell area below either treatment alone...
March 24, 2017: Scientific Reports
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