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Article ; Online: Exciting New Developments and Emerging Themes in Glycosaminoglycan Research.

Merry, Catherine L R

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society

2020 Volume 69, Issue 1, Page(s) 9–11

Abstract: In times where many people have suffered loss and others of us are dealing with stress, disruption, and fear, there is a lot of comfort to be taken in reading. If we are not able to meet up and discuss our work in person, exploring published studies ... ...

Abstract	In times where many people have suffered loss and others of us are dealing with stress, disruption, and fear, there is a lot of comfort to be taken in reading. If we are not able to meet up and discuss our work in person, exploring published studies provides some succor, even without the cheese, wine, and other traditions of our usual get-togethers. Fortunately, recent months have seen many high-quality papers around the topic of glycosaminoglycans. I can only pick up on a very few here, those that I have particularly enjoyed, but the following collection of reviews will also be a treat and hopefully tide us over until our research community can regroup.
MeSH term(s)	Animals ; Biosynthetic Pathways ; Chondroitin Sulfate Proteoglycans/metabolism ; Glycocalyx/metabolism ; Glycosaminoglycans/metabolism ; Heparitin Sulfate/metabolism ; Humans ; Hyaluronan Synthases/metabolism ; Hyaluronic Acid/metabolism ; Proteoglycans/metabolism ; Uridine Diphosphate Glucose Dehydrogenase/metabolism
Chemical Substances	Chondroitin Sulfate Proteoglycans ; Glycosaminoglycans ; Proteoglycans ; Hyaluronic Acid (9004-61-9) ; Heparitin Sulfate (9050-30-0) ; Uridine Diphosphate Glucose Dehydrogenase (EC 1.1.1.22) ; Hyaluronan Synthases (EC 2.4.1.212)
Language	English
Publishing date	2020-11-12
Publishing country	United States
Document type	Introductory Journal Article
ZDB-ID	218208-7
ISSN	1551-5044 ; 0022-1554
ISSN (online)	1551-5044
ISSN	0022-1554
DOI	10.1369/0022155420974361
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Article ; Online: Application of a 3D hydrogel-based model to replace use of animals for passaging patient-derived xenografts.

Jones, Sal / Ashworth, Jennifer C / Meakin, Marian / Collier, Pamela / Probert, Catherine / Ritchie, Alison A / Merry, Catherine L R / Grabowska, Anna M

In vitro models

2023 Volume 2, Issue 3-4, Page(s) 99–111

Abstract: Purpose: This 3D in vitro cancer model for propagation of patient-derived cells, using a synthetic self-assembling peptide gel, allows the formation of a fully characterised, tailorable tumour microenvironment. Unlike many existing 3D cancer models, the ...

Abstract	Purpose: This 3D in vitro cancer model for propagation of patient-derived cells, using a synthetic self-assembling peptide gel, allows the formation of a fully characterised, tailorable tumour microenvironment. Unlike many existing 3D cancer models, the peptide gel is inert, apart from molecules and motifs deliberately added or produced by cells within the model. Methods: Breast cancer patient-derived xenografts (PDXs) were disaggregated and embedded in a peptide hydrogel. Growth was monitored by microscopic examination and at intervals, cells were extracted from the gels and passaged on into fresh gels. Passaged cells were assessed by qPCR and immunostaining techniques for the retention of characteristic markers. Results: Breast cancer PDXs were shown to be capable of expansion over four or more passages in the peptide gel. Contaminating mouse cells were found to be rapidly removed by successive passages. The resulting human cells were shown to be compatible with a range of common assays useful for assessing survival, growth and maintenance of heterogeneity. Conclusions: Based on these findings, the hydrogel has the potential to provide an effective and practical breast cancer model for the passage of PDXs which will have the added benefits of being relatively cheap, fully-defined and free from the use of animals or animal products. Encapsulated cells will require further validation to confirm the maintenance of cell heterogeneity, genotypes and phenotypes across passage, but with further development, including the addition of bespoke cell and matrix components of the tumour microenvironment, there is clear potential to model other cancer types. Supplementary information: The online version contains supplementary material available at 10.1007/s44164-023-00048-x.
Language	English
Publishing date	2023-05-09
Publishing country	Switzerland
Document type	Journal Article
ISSN	2731-3441
ISSN (online)	2731-3441
DOI	10.1007/s44164-023-00048-x
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Article ; Online: High sensitivity analysis of nanogram quantities of glycosaminoglycans using ToF-SIMS.

Hook, Andrew L / Hogwood, John / Gray, Elaine / Mulloy, Barbara / Merry, Catherine L R

Communications chemistry

2021 Volume 4, Issue 1, Page(s) 67

Abstract: Glycosaminoglycans (GAGs) are important biopolymers that differ in the sequence of saccharide units and in post polymerisation alterations at various positions, making these complex molecules challenging to analyse. Here we describe an approach that ... ...

Abstract	Glycosaminoglycans (GAGs) are important biopolymers that differ in the sequence of saccharide units and in post polymerisation alterations at various positions, making these complex molecules challenging to analyse. Here we describe an approach that enables small quantities (<200 ng) of over 400 different GAGs to be analysed within a short time frame (3-4 h). Time of flight secondary ion mass spectrometry (ToF-SIMS) together with multivariate analysis is used to analyse the entire set of GAG samples. Resultant spectra are derived from the whole molecules and do not require pre-digestion. All 6 possible GAG types are successfully discriminated, both alone and in the presence of fibronectin. We also distinguish between pharmaceutical grade heparin, derived from different animal species and from different suppliers, to a sensitivity as low as 0.001 wt%. This approach is likely to be highly beneficial in the quality control of GAGs produced for therapeutic applications and for characterising GAGs within biomaterials or from in vitro cell culture.
Language	English
Publishing date	2021-05-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2929562-2
ISSN	2399-3669 ; 2399-3669
ISSN (online)	2399-3669
ISSN	2399-3669
DOI	10.1038/s42004-021-00506-1
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Article ; Online: Hydrogel-Based Pre-Clinical Evaluation of Repurposed FDA-Approved Drugs for AML.

James, Jenna R / Curd, Johnathan / Ashworth, Jennifer C / Abuhantash, Mays / Grundy, Martin / Seedhouse, Claire H / Arkill, Kenton P / Wright, Amanda J / Merry, Catherine L R / Thompson, Alexander

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: In vivo models of acute myeloid leukemia (AML) are low throughput, and standard liquid culture models fail to recapitulate the mechanical and biochemical properties of the extracellular matrix-rich protective bone marrow niche that contributes to drug ... ...

Abstract	In vivo models of acute myeloid leukemia (AML) are low throughput, and standard liquid culture models fail to recapitulate the mechanical and biochemical properties of the extracellular matrix-rich protective bone marrow niche that contributes to drug resistance. Candidate drug discovery in AML requires advanced synthetic platforms to improve our understanding of the impact of mechanical cues on drug sensitivity in AML. By use of a synthetic, self-assembling peptide hydrogel (SAPH) of modifiable stiffness and composition, a 3D model of the bone marrow niche to screen repurposed FDA-approved drugs has been developed and utilized. AML cell proliferation was dependent on SAPH stiffness, which was optimized to facilitate colony growth. Three candidate FDA-approved drugs were initially screened against the THP-1 cell line and mAF9 primary cells in liquid culture, and EC50 values were used to inform drug sensitivity assays in the peptide hydrogel models. Salinomycin demonstrated efficacy in both an 'early-stage' model in which treatment was added shortly after initiation of AML cell encapsulation, and an 'established' model in which time-encapsulated cells had started to form colonies. Sensitivity to Vidofludimus treatment was not observed in the hydrogel models, and Atorvastatin demonstrated increased sensitivity in the 'established' compared to the 'early-stage' model. AML patient samples were equally sensitive to Salinomycin in the 3D hydrogels and partially sensitive to Atorvastatin. Together, this confirms that AML cell sensitivity is drug- and context-specific and that advanced synthetic platforms for higher throughput are valuable tools for pre-clinical evaluation of candidate anti-AML drugs.
MeSH term(s)	Humans ; Hydrogels/therapeutic use ; Atorvastatin/therapeutic use ; Leukemia, Myeloid, Acute/metabolism ; Bone Marrow/metabolism ; Peptides/therapeutic use
Chemical Substances	Hydrogels ; Atorvastatin (A0JWA85V8F) ; Peptides
Language	English
Publishing date	2023-02-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24044235
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Article ; Online: OptoRheo: Simultaneous in situ micro-mechanical sensing and imaging of live 3D biological systems.

Mendonca, Tania / Lis-Slimak, Katarzyna / Matheson, Andrew B / Smith, Matthew G / Anane-Adjei, Akosua B / Ashworth, Jennifer C / Cavanagh, Robert / Paterson, Lynn / Dalgarno, Paul A / Alexander, Cameron / Tassieri, Manlio / Merry, Catherine L R / Wright, Amanda J

Communications biology

2023 Volume 6, Issue 1, Page(s) 463

Abstract: Biomechanical cues from the extracellular matrix (ECM) are essential for directing many cellular processes, from normal development and repair, to disease progression. To better understand cell-matrix interactions, we have developed a new instrument ... ...

Abstract	Biomechanical cues from the extracellular matrix (ECM) are essential for directing many cellular processes, from normal development and repair, to disease progression. To better understand cell-matrix interactions, we have developed a new instrument named 'OptoRheo' that combines light sheet fluorescence microscopy with particle tracking microrheology. OptoRheo lets us image cells in 3D as they proliferate over several days while simultaneously sensing the mechanical properties of the surrounding extracellular and pericellular matrix at a sub-cellular length scale. OptoRheo can be used in two operational modalities (with and without an optical trap) to extend the dynamic range of microrheology measurements. We corroborated this by characterising the ECM surrounding live breast cancer cells in two distinct culture systems, cell clusters in 3D hydrogels and spheroids in suspension culture. This cutting-edge instrument will transform the exploration of drug transport through complex cell culture matrices and optimise the design of the next-generation of disease models.
MeSH term(s)	Extracellular Matrix ; Microscopy, Fluorescence ; Hydrogels ; Cell Communication
Chemical Substances	Hydrogels
Language	English
Publishing date	2023-04-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-023-04780-8
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Article: The Good the Bad and the Ugly of Glycosaminoglycans in Tissue Engineering Applications.

Ayerst, Bethanie I / Merry, Catherine L R / Day, Anthony J

Pharmaceuticals (Basel, Switzerland)

2017 Volume 10, Issue 2

Abstract: High sulfation, low cost, and the status of heparin as an already FDA- and EMA- approved product, mean that its inclusion in tissue engineering (TE) strategies is becoming increasingly popular. However, the use of heparin may represent a naïve approach. ... ...

Abstract	High sulfation, low cost, and the status of heparin as an already FDA- and EMA- approved product, mean that its inclusion in tissue engineering (TE) strategies is becoming increasingly popular. However, the use of heparin may represent a naïve approach. This is because tissue formation is a highly orchestrated process, involving the temporal expression of numerous growth factors and complex signaling networks. While heparin may enhance the retention and activity of certain growth factors under particular conditions, its binding 'promiscuity' means that it may also inhibit other factors that, for example, play an important role in tissue maintenance and repair. Within this review we focus on articular cartilage, highlighting the complexities and highly regulated processes that are involved in its formation, and the challenges that exist in trying to effectively engineer this tissue. Here we discuss the opportunities that glycosaminoglycans (GAGs) may provide in advancing this important area of regenerative medicine, placing emphasis on the need to move away from the common use of heparin, and instead focus research towards the utility of specific GAG preparations that are able to modulate the activity of growth factors in a more controlled and defined manner, with less off-target effects.
Language	English
Publishing date	2017-06-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph10020054
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Article ; Online: The biochemical determinants of tissue regeneration.

Giangreco, Adam / Merry, Catherine L R

Biochemical Society transactions

2014 Volume 42, Issue 3, Page(s) 607–608

Abstract: The field of regenerative medicine offers tantalizing hope for the repair and replacement of damaged organs and tissues, with the ultimate goal of restoring normal tissue function. This field represents an enormous range of biological, chemical and ... ...

Abstract	The field of regenerative medicine offers tantalizing hope for the repair and replacement of damaged organs and tissues, with the ultimate goal of restoring normal tissue function. This field represents an enormous range of biological, chemical and biophysical technologies that harness the restorative properties of living materials, especially human cells, to produce new molecular and cellular medicines, diagnostics, devices and healthcare research tools. The goal of this Biochemical Society Annual Symposium was to explore the key biochemical determinants of tissue regeneration, and we highlight the contribution of biochemistry to this emerging field of regenerative medicine.
MeSH term(s)	Biochemistry ; Humans ; Regenerative Medicine
Language	English
Publishing date	2014-05-21
Publishing country	England
Document type	Journal Article
ZDB-ID	184237-7
ISSN	1470-8752 ; 0300-5127
ISSN (online)	1470-8752
ISSN	0300-5127
DOI	10.1042/BST20140095
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Book ; Conference proceedings: Biochemical determinants of tissue regeneration

Giangreco, Adam / Merry, Catherine L. R

(Biochemical Society symposia, ; no. 81)

2014

Institution	Biochemical Society (Great Britain). / Symposium Biochemical Society (Great Britain),
Author's details	organized and edited by Adam Giangreco and Catherine L.R. Merry
Series title	Biochemical Society symposia, ; no. 81
MeSH term(s)	Regeneration ; Cell Engineering
Language	English
Dates of publication	2014-2014
Size	xi, 133 pages :, illustrations ;, 26 cm.
Document type	Book ; Conference proceedings
Note	"BSSYAT 81"--Cover.
ISBN	9781855781962 ; 1855781964
Database	Catalogue of the US National Library of Medicine (NLM)

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Article ; Online: Selective Inhibition of Heparan Sulphate and Not Chondroitin Sulphate Biosynthesis by a Small, Soluble Competitive Inhibitor.

Maciej-Hulme, Marissa L / Dubaissi, Eamon / Shao, Chun / Zaia, Joseph / Amaya, Enrique / Flitsch, Sabine L / Merry, Catherine L R

International journal of molecular sciences

2021 Volume 22, Issue 13

Abstract: The glycosaminoglycan, heparan sulphate (HS), orchestrates many developmental processes. Yet its biological role has not yet fully been elucidated. Small molecule chemical inhibitors can be used to perturb HS function and these compounds provide cheap ... ...

Abstract	The glycosaminoglycan, heparan sulphate (HS), orchestrates many developmental processes. Yet its biological role has not yet fully been elucidated. Small molecule chemical inhibitors can be used to perturb HS function and these compounds provide cheap alternatives to genetic manipulation methods. However, existing chemical inhibition methods for HS also interfere with chondroitin sulphate (CS), complicating data interpretation of HS function. Herein, a simple method for the selective inhibition of HS biosynthesis is described. Using endogenous metabolic sugar pathways, Ac
MeSH term(s)	Animals ; Biosynthetic Pathways/drug effects ; CHO Cells ; Carbohydrate Metabolism/drug effects ; Chondroitin Sulfates/biosynthesis ; Chondroitin Sulfates/chemistry ; Cricetulus ; Drug Discovery ; Glycosaminoglycans/biosynthesis ; Heparitin Sulfate/biosynthesis ; Heparitin Sulfate/chemistry
Chemical Substances	Glycosaminoglycans ; Chondroitin Sulfates (9007-28-7) ; Heparitin Sulfate (9050-30-0)
Language	English
Publishing date	2021-06-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22136988
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Article ; Online: Perlecan (HSPG2) promotes structural, contractile, and metabolic development of human cardiomyocytes.

Johnson, Benjamin B / Cosson, Marie-Victoire / Tsansizi, Lorenza I / Holmes, Terri L / Gilmore, Tegan / Hampton, Katherine / Song, Ok-Ryul / Vo, Nguyen T N / Nasir, Aishah / Chabronova, Alzbeta / Denning, Chris / Peffers, Mandy J / Merry, Catherine L R / Whitelock, John / Troeberg, Linda / Rushworth, Stuart A / Bernardo, Andreia S / Smith, James G W

Cell reports

2024 Volume 43, Issue 1, Page(s) 113668

Abstract: Perlecan (HSPG2), a heparan sulfate proteoglycan similar to agrin, is key for extracellular matrix (ECM) maturation and stabilization. Although crucial for cardiac development, its role remains elusive. We show that perlecan expression increases as ... ...

Abstract	Perlecan (HSPG2), a heparan sulfate proteoglycan similar to agrin, is key for extracellular matrix (ECM) maturation and stabilization. Although crucial for cardiac development, its role remains elusive. We show that perlecan expression increases as cardiomyocytes mature in vivo and during human pluripotent stem cell differentiation to cardiomyocytes (hPSC-CMs). Perlecan-haploinsuffient hPSCs (HSPG2
MeSH term(s)	Humans ; Heparan Sulfate Proteoglycans/genetics ; Heparan Sulfate Proteoglycans/metabolism ; Agrin/metabolism ; Myocytes, Cardiac/metabolism ; Extracellular Matrix/metabolism ; Extracellular Matrix Proteins/metabolism
Chemical Substances	perlecan (143972-95-6) ; Heparan Sulfate Proteoglycans ; Agrin ; Extracellular Matrix Proteins
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.113668
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