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Extra cellular matrix

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https://www.readbyqxmd.com/read/28414242/discovery-of-2-2-ethyl-6-4-2-3-hydroxyazetidin-1-yl-2-oxo-ethyl-piperazin-1-yl-8-methyl-imidazo-1-2-a-pyridin-3-yl-methyl-amino-4-4-fluorophenyl-thiazole-5-carbonitrile-glpg1690-a-first-in-class-autotaxin-inhibitor-undergoing-clinical-evaluation-for-the-treatment
#1
Nicolas Desroy, Christopher Housseman, Xavier Bock, Agnès Joncour, Natacha Bienvenu, Laëtitia Cherel, Virginie Labeguere, Emilie Rondet, Christophe Peixoto, Jean-Marie Joël Grassot, Olivier Picolet, Denis Annoot, Nicolas Triballeau, Alain Monjardet, Emanuelle Wakselman, Veronique Roncoroni, Sandrine Le Tallec, Roland Blanque, Celine Cottereaux, Nele Vandervoort, Thierry Christophe, Patrick Mollat, Marieke B A C Lamers, Marielle Auberval, Boska Hrvacic, Jovica Ralic, Line Oste, Ellen Van der Aar, Reginald Brys, Bertrand Heckmann
Autotaxin is a circulating enzyme with a major role in the production of lysophosphatic acid (LPA) species in blood. A role for the autotaxin/LPA axis has been suggested in many disease areas including pulmonary fibrosis. Structural modifications of the known autotaxin inhibitor lead compound 1, to attenuate hERG inhibition, remove CYP3A4 time-dependent inhibition and improve pharmacokinetic properties, led to the identification of clinical candidate GLPG1690 (11). Compound 11 was able to cause a sustained reduction of LPA levels in plasma in vivo and was shown to be efficacious in a bleomycin-induced pulmonary fibrosis model in mice, and in reducing extra-cellular matrix deposition in the lung whilst also reducing LPA 18:2 content in bronchoalveolar lavage fluid...
April 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28413347/a-biochemo-mechano-coupled-computational-model-combining-membrane-transport-and-pericellular-proteolysis-in-tissue-mechanics
#2
A-T Vuong, A D Rauch, W A Wall
We present a computational model for the interaction of surface- and volume-bound scalar transport and reaction processes with a deformable porous medium. The application in mind is pericellular proteolysis, i.e. the dissolution of the solid phase of the extracellular matrix (ECM) as a response to the activation of certain chemical species at the cell membrane and in the vicinity of the cell. A poroelastic medium model represents the extra cellular scaffold and the interstitial fluid flow, while a surface-bound transport model accounts for the diffusion and reaction of membrane-bound chemical species...
March 2017: Proceedings. Mathematical, Physical, and Engineering Sciences
https://www.readbyqxmd.com/read/28374979/matrix-metalloproteinase-mmp-2-activity-is-associated-with-divergent-regulation-of-calponin-1-in-conductance-and-resistance-arteries-in-hypertension-induced-early-vascular-dysfunction-and-remodelling
#3
Juliana M Parente, Camila A Pereira, Gustavo H Oliveira-Paula, José Eduardo Tanus-Santos, Rita C Tostes, Michele M Castro
Matrix metalloproteinase (MMP)-2 participates in hypertension-induced maladaptive vascular remodelling by degrading extra and intracellular proteins. The consequent extracellular matrix rearrangement and phenotype switch of vascular smooth muscle cells (VSMC) lead to increased cellular migration and proliferation. As calponin-1 degradation by MMP-2 may lead to VSMC proliferation during hypertension, the hypothesis of this study is that increased MMP-2 activity contributes to early hypertension-induced maladaptive remodelling in conductance and resistance arteries via regulation of calponin-1...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28372287/organ-reconstruction-dream-or-reality-for%C3%A2-the%C3%A2-future
#4
J-F Stoltz, L Zhang, J S Ye, N De Isla
The relevance of research on reconstructed organs is justified by the lack of organs available for transplant and the growing needs for the ageing population. The development of a reconstructed organ involves two parallel complementary steps: de-cellularization of the organ with the need to maintain the structural integrity of the extracellular matrix and vascular network and re-cellularization of the scaffold with stem cells or resident cells.Whole organ engineering for liver, heart, lung or kidneys, is particularly difficult because of the structural complexity of organs and heterogeneity of cells...
2017: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/28371753/a-microfluidic-platform-for-drug-screening-in-a-3d-cancer-microenvironment
#5
Hardik J Pandya, Karan Dhingra, Devbalaji Prabhakar, Vineethkrishna Chandrasekar, Siva Kumar Natarajan, Anish S Vasan, Ashish Kulkarni, Hadi Shafiee
Development of resistance to chemotherapy treatments is a major challenge in the battle against cancer. Although a vast repertoire of chemotherapeutics is currently available for treating cancer, a technique for rapidly identifying the right drug based on the chemo-resistivity of the cancer cells is not available and it currently takes weeks to months to evaluate the response of cancer patients to a drug. A sensitive, low-cost diagnostic assay capable of rapidly evaluating the effect of a series of drugs on cancer cells can significantly change the paradigm in cancer treatment management...
March 27, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28367247/fibronectin-how-its-aberrant-expression-in-tumors-may-improve-therapeutic-targeting
#6
REVIEW
Jennifer Peyling Wang, Abigail Hielscher
Fibronectin is a matrix glycoprotein which has not only been found to be over-expressed in several cancers, but has been shown to participate in several steps of tumorigenesis. The purpose of this review is to illustrate how aberrant fibronectin expression influences tumor growth, invasion, metastasis and therapy resistance. In particular, this review will focus on the interactions between cell receptor ligands and fibronectin and how this interaction influences downstream signaling events that aid tumor progression...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28365358/rapid-and-short-term-extra-cellular-matrix-mediated-in-vitro-culturing-of-tumor-and-non-tumor-human-primary-prostate-cells-from-fresh-radical-prostatectomy-tissue
#7
Ashok C Chander, Michael S Manak, Jonathan S Varsanik, Brad J Hogan, Vladimir Mouraviev, Stephen M Zappala, Grannum R Sant, David M Albala
OBJECTIVE: To culture prostate cells from fresh biopsy core samples from radical prostatectomy tissue. Further, given the genetic heterogeneity of prostate cells, the ability to culture single cells from primary prostate tissue may be of importance towards enabling single-cell characterization of primary prostate tissue via molecular and cellular phenotypic biomarkers. METHODS: 260 consecutive tissue samples from radical prostatectomies (RP) were collected between October 2014 and January 2016, transported at 4(o) C in serum free media to an off-site central laboratory, dissociated, and cultured...
March 29, 2017: Urology
https://www.readbyqxmd.com/read/28358123/molecular-therapy-for-degenerative-disc-disease-clues-from-secretome-analysis-of-the-notochordal-cell-rich-nucleus-pulposus
#8
Ajay Matta, M Zia Karim, David E Isenman, W Mark Erwin
Degenerative disc disease (DDD) is associated with spinal pain often leading to long-term disability. However, the non-chondrodystrophic canine intervertebral disc is protected from the development of DDD, ostensibly due to its retention of notochordal cells (NC) in the nucleus pulposus (NP). In this study, we hypothesized that secretome analysis of the NC-rich NP will lead to the identification of key proteins that delay the onset of DDD. Using mass-spectrometry, we identified 303 proteins including components of TGFβ- and Wnt-signaling, anti-angiogeneic factors and proteins that inhibit axonal ingrowth in the bioactive fractions of serum free, notochordal cell derived conditioned medium (NCCM)...
March 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28357075/de-novo-systemic-deleterious-amino-acid-substitutions-are-common-in-large-cytoskeleton-related-protein-coding-regions
#9
Rebecca J Stoll, Grace R Thompson, Mohammad D Samy, George Blanck
Human mutagenesis is largely random, thus large coding regions, simply on the basis of probability, represent relatively large mutagenesis targets. Thus, we considered the possibility that large cytoskeletal-protein related coding regions (CPCRs), including extra-cellular matrix (ECM) coding regions, would have systemic nucleotide variants that are not present in common SNP databases. Presumably, such variants arose recently in development or in recent, preceding generations. Using matched breast cancer and blood-derived normal datasets from the cancer genome atlas, CPCR single nucleotide variants (SNVs) not present in the All SNPs(142) or 1000 Genomes databases were identified...
February 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28298487/tgf-%C3%AE-triggers-rapid-fibrillogenesis-via-a-novel-t%C3%AE-rii-dependent-fibronectin-trafficking-mechanism
#10
Archana Varadaraj, Laura M Jenkins, Priyanka Singh, Anindya Chanda, John Snider, N Y Lee, Ayelet R Amsalem-Zafran, Marcelo Ehrlich, Yoav I Henis, Karthikeyan Mythreye
Fibronectin (FN) is a critical regulator of extra cellular matrix (ECM) remodeling through its availability and stepwise polymerization for fibrillogenesis. Availability of FN is regulated by its synthesis and turnover, while fibrillogenesis is a multistep integrin dependent process essential for cell migration, proliferation and tissue function. Transforming growth factor beta (TGF-β) is an established regulator of ECM remodeling through transcriptional control of ECM proteins. Here, we show that TGF-β, through increased FN trafficking in a transcription and SMAD independent manner, is a direct and rapid inducer of fibrillogenesis required for TGF-β induced cell migration...
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28287547/spatiotemporal-analysis-of-cytokinetic-events-in-fission-yeast
#11
Bin Wei, Brian S Hercyk, Julius Habiyaremye, Maitreyi Das
Cytokinesis, the final step in cell division is critical for maintaining genome integrity. Proper cytokinesis is important for cell differentiation and development. Cytokinesis involves a series of events that are well coordinated in time and space. Cytokinesis involves the formation of an actomyosin ring at the division site, followed by ring constriction, membrane furrow formation and extra cellular matrix remodeling. The fission yeast, Schizosaccharomyces pombe (S. pombe) is a well-studied model system that has revealed with substantial clarity the initial events in cytokinesis...
February 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28277889/soft-hydrogels-featuring-in-depth-surface-density-gradients-for-the-simple-establishment-of-3d-tissue-models-for-screening-applications
#12
Ning Zhang, Vincent Milleret, Greta Thompson-Steckel, Ning-Ping Huang, János Vörös, Benjamin R Simona, Martin Ehrbar
Three-dimensional (3D) cell culture models are gaining increasing interest for use in drug development pipelines due to their closer resemblance to human tissues. Hydrogels are the first-choice class of materials to recreate in vitro the 3D extra-cellular matrix (ECM) environment, important in studying cell-ECM interactions and 3D cellular organization and leading to physiologically relevant in vitro tissue models. Here we propose a novel hydrogel platform consisting of a 96-well plate containing pre-cast synthetic PEG-based hydrogels for the simple establishment of 3D (co-)culture systems without the need for the standard encapsulation method...
March 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28269209/three-dimensional-graphene-scaffold-for-cardiac-tissue-engineering-and-in-situ-electrical-recording
#13
S K Ameri, P K Singh, R D'Angelo, W Stoppel, L Black, S R Sonkusale
In this paper, we present a three-dimensional graphene foam made of few layers of CVD grown graphene as a scaffold for growing cardiac cells and recording their electrical activity. Our results show that graphene foam not only provides an excellent extra-cellular matrix (ECM) for the culture of such electrogenic cells but also enables recording of its extracellular electrical activity in-situ. Recording is possible due to graphene's excellent conductivity. In this paper, we present our results on the fabrication of the graphene scaffold and initial studies on the culture of cardiac cell lines such as HL-1 and recording of their real-time electrical activity...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28267799/on-the-adhesion-cohesion-balance-and-oxygen-consumption-characteristics-of-liver-organoids
#14
Giorgio Mattei, Chiara Magliaro, Serena Giusti, Sarada Devi Ramachandran, Stefan Heinz, Joris Braspenning, Arti Ahluwalia
Liver organoids (LOs) are of interest in tissue replacement, hepatotoxicity and pathophysiological studies. However, it is still unclear what triggers LO self-assembly and what the optimal environment is for their culture. Hypothesizing that LO formation occurs as a result of a fine balance between cell-substrate adhesion and cell-cell cohesion, we used 3 cell types (hepatocytes, liver sinusoidal endothelial cells and mesenchymal stem cells) to investigate LO self-assembly on different substrates keeping the culture parameters (e...
2017: PloS One
https://www.readbyqxmd.com/read/28253271/the-association-between-osteopontin-gene-polymorphisms-osteopontin-expression-and-sarcoidosis
#15
Hadas Lavi, Miri Assayag, Assaf Schwartz, Nissim Arish, Zvi G Fridlender, Neville Berkman
BACKGROUND: Sarcoidosis is a systemic inflammatory disease of unknown etiology. Osteopontin (SPP1, OPN) is an extra cellular matrix glycoprotein and cytokine with a known role in granuloma formation and in autoimmune and inflammatory diseases. OBJECTIVE: To determine whether plasma OPN levels are elevated in patients with sarcoidosis and compare the frequency of four single nucleotide polymorphism (SNPs) variants in the OPN gene in sarcoidosis patients compared to healthy controls...
2017: PloS One
https://www.readbyqxmd.com/read/28242376/cell-based-therapeutics-in-type-1-diabetes-mellitus
#16
Fernanda Zamboni, Maurice N Collins
This review focuses on Type 1 diabetes mellitus (T1DM) and the role of bioengineering, nanotechnology and cell therapy in its treatment. T1DM is discussed in terms of its prevalence as well as the role of the extra cellular matrix (ECM) of the pancreas in its development and mode of action. Surface engineering strategies and the chemistries behind important cell encapsulation techniques, which are emerging from recent research in immunosuppression, are described. Key enabling technologies such as therapeutic agent immobilization on cells, oxygen releasing systems, gene delivery and bio imaging are assessed with respect to T1DM...
February 27, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28231262/oleanolic-acid-induces-migration-in-mv1lu-and-mda-mb-231-epithelial-cells-involving-egf-receptor-and-map-kinases-activation
#17
Ángel Bernabé-García, David Armero-Barranco, Sergio Liarte, María Ruzafa-Martínez, Antonio Jesús Ramos-Morcillo, Francisco José Nicolás
During wound healing, skin function is restored by the action of several cell types that undergo differentiation, migration, proliferation and/or apoptosis. These dynamics are tightly regulated by the evolution of the extra cellular matrix (ECM) contents along the process. Pharmacologically active flavonoids have shown to exhibit useful physiological properties interesting in pathological states. Among them, oleanolic acid (OA), a pentacyclic triterpene, shows promising properties over wound healing, as increased cell migration in vitro and improved wound resolution in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28228548/contact-guidance-requires-spatial-control-of-leading-edge-protrusion
#18
G R Ramirez-San Juan, P W Oakes, M L Gardel
In vivo, geometric cues from the extracellular matrix (ECM) are critical for the regulation of cell shape, adhesion, and migration. During contact guidance, the fibrillar architecture of the ECM promotes an elongated cell shape and migration along the fibrils. The subcellular mechanisms by which cells sense ECM geometry and translate it into changes in shape and migration direction are not understood. Here we pattern linear fibronectin features to mimic fibrillar ECM and elucidate the mechanisms of contact guidance...
April 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28227439/three-dimensional-graphene-scaffold-for-cardiac-tissue-engineering-and-in-situ-electrical-recording
#19
S K Ameri, P K Singh, R D'Angelo, W Stoppel, L Black, S R Sonkusale, S K Ameri, P K Singh, R D'Angelo, W Stoppel, L Black, S R Sonkusale, L Black, P K Singh, W Stoppel, S R Sonkusale, R D'Angelo, S K Ameri
In this paper, we present a three-dimensional graphene foam made of few layers of CVD grown graphene as a scaffold for growing cardiac cells and recording their electrical activity. Our results show that graphene foam not only provides an excellent extra-cellular matrix (ECM) for the culture of such electrogenic cells but also enables recording of its extracellular electrical activity in-situ. Recording is possible due to graphene's excellent conductivity. In this paper, we present our results on the fabrication of the graphene scaffold and initial studies on the culture of cardiac cell lines such as HL-1 and recording of their real-time electrical activity...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28221758/synthesis-and-fabrication-of-collagen-coated-ostholamide-electrospun-nanofiber-scaffold-for-wound-healing
#20
Subramani Kandhasamy, Sathiamurthi Perumal, Balaraman Madhan, Narayanan Umamaheswari, Javid 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 electrospun nanofibers. Initially, ostholamide (OSA) was synthesized from osthole (a natural coumarin), characterized by (1)H, (13)C, DEPT-135 NMR, ESI-MS, and FT-IR spectroscopy analysis. OSA was incorporated into polyhydroxybutyrate (PHB) and gelatin (GEL), which serve as templates for electrospun nanofibers. The coating of OSA-PHB-GEL nanofibers with collagen resulted in PHB-GEL-OSA-COL nanofibrous scaffold which mimics extracellular matrix and serves as an effective biomaterial for tissue engineering applications, especially for wound healing...
March 1, 2017: ACS Applied Materials & Interfaces
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