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Article ; Online: miRetrieve-an R package and web application for miRNA text mining.

Friedrich, Julian / Hammes, Hans-Peter / Krenning, Guido

NAR genomics and bioinformatics

2021 Volume 3, Issue 4, Page(s) lqab117

Abstract: microRNAs (miRNAs) regulate gene expression and thereby influence biological processes in health and disease. As a consequence, miRNAs are intensely studied and literature on miRNAs has been constantly growing. While this growing body of literature ... ...

Abstract	microRNAs (miRNAs) regulate gene expression and thereby influence biological processes in health and disease. As a consequence, miRNAs are intensely studied and literature on miRNAs has been constantly growing. While this growing body of literature reflects the interest in miRNAs, it generates a challenge to maintain an overview, and the comparison of miRNAs that may function across diverse disease fields is complex due to this large number of relevant publications. To address these challenges, we designed miRetrieve, an R package and web application that provides an overview on miRNAs. By text mining, miRetrieve can characterize and compare miRNAs within specific disease fields and across disease areas. This overview provides focus and facilitates the generation of new hypotheses. Here, we explain how miRetrieve works and how it is used. Furthermore, we demonstrate its applicability in an exemplary case study and discuss its advantages and disadvantages.
Language	English
Publishing date	2021-12-23
Publishing country	England
Document type	Journal Article
ISSN	2631-9268
ISSN (online)	2631-9268
DOI	10.1093/nargab/lqab117
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The Endothelium as a Target for Anti-Atherogenic Therapy: A Focus on the Epigenetic Enzymes EZH2 and SIRT1.

Fledderus, Jolien / Vanchin, Byambasuren / Rots, Marianne G / Krenning, Guido

Journal of personalized medicine

2021 Volume 11, Issue 2

Abstract: Endothelial cell inflammatory activation and dysfunction are key events in the pathophysiology of atherosclerosis, and are associated with an elevated risk of cardiovascular events. Yet, therapies specifically targeting the endothelium and ... ...

Abstract	Endothelial cell inflammatory activation and dysfunction are key events in the pathophysiology of atherosclerosis, and are associated with an elevated risk of cardiovascular events. Yet, therapies specifically targeting the endothelium and atherosclerosis are lacking. Here, we review how endothelial behaviour affects atherogenesis and pose that the endothelium may be an efficacious cellular target for antiatherogenic therapies. We discuss the contribution of endothelial inflammatory activation and dysfunction to atherogenesis and postulate that the dysregulation of specific epigenetic enzymes, EZH2 and SIRT1, aggravate endothelial dysfunction in a pleiotropic fashion. Moreover, we propose that commercially available drugs are available to clinically explore this postulation.
Language	English
Publishing date	2021-02-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm11020103
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Article ; Online: Endothelial function after the exposition of magnesium degradation products.

Echeverry-Rendón, Mónica / Echeverria, Felix / Buikema, Hendrik / Harmsen, Martin C / Krenning, Guido

Biomaterials advances

2022 Volume 134, Page(s) 112693

Abstract: One of the most common magnesium (Mg) applications in the biomedical field is in cardiovascular stents. Although Mg is an essential element for homeostasis, Mg is highly reactive, and locally high Mg concentrations can have toxic effects on the ... ...

Abstract	One of the most common magnesium (Mg) applications in the biomedical field is in cardiovascular stents. Although Mg is an essential element for homeostasis, Mg is highly reactive, and locally high Mg concentrations can have toxic effects on the surrounding tissue. One strategy to circumvent the Mg toxicity is using coatings or surface modifications that prevent the leaching of excessive Mg ions. In the current study, commercially pure magnesium (c.p Mg) was modified through plasma electrolytic oxidation (PEO) to produce a protective coating primarily composed of Mg oxide (MgO) and Mg hydroxide (Mg(OH)
MeSH term(s)	Alloys/pharmacology ; Animals ; Coated Materials, Biocompatible/pharmacology ; Human Umbilical Vein Endothelial Cells ; Humans ; Magnesium/pharmacology ; Magnesium Hydroxide ; Magnesium Oxide ; Swine
Chemical Substances	Alloys ; Coated Materials, Biocompatible ; Magnesium Oxide (3A3U0GI71G) ; Magnesium (I38ZP9992A) ; Magnesium Hydroxide (NBZ3QY004S)
Language	English
Publishing date	2022-02-08
Publishing country	Netherlands
Document type	Journal Article
ISSN	2772-9508
ISSN (online)	2772-9508
DOI	10.1016/j.msec.2022.112693
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Article ; Online: Impact of the -1T>C single-nucleotide polymorphism of the CD40 gene on the development of endothelial dysfunction in a pro-diabetic microenvironment.

Joshi, Pooja / Mohr, Franziska / Rumig, Cordula / Kliemank, Elisabeth / Krenning, Guido / Kopf, Stefan / Hecker, Markus / Wagner, Andreas H

Atherosclerosis

2023 , Page(s) 117386

Abstract: Background and aims: Hyperglycemia reinforces pro-inflammatory conditions that enhance CD40 expression in endothelial cells (EC). Thymine to cytosine transition (-1T > C) in the promoter of the CD40 gene (rs1883832) further increases the abundance of ... ...

Abstract	Background and aims: Hyperglycemia reinforces pro-inflammatory conditions that enhance CD40 expression in endothelial cells (EC). Thymine to cytosine transition (-1T > C) in the promoter of the CD40 gene (rs1883832) further increases the abundance of CD40 protein on the EC surface. This study examines potential associations of the -1T > C SNP of the CD40 gene with type 1 (T1D) or type 2 (T2D) diabetes. Moreover, it investigates the impact of a pro-inflammatory diabetic microenvironment on gene expression in human cultured umbilical vein EC (HUVEC) derived from CC- vs. TT-genotype donors. Methods: Tetra-ARMS-PCR was used to compare genotype distribution in 252 patients with diabetes. Soluble CD40 ligand (sCD40L) and soluble CD40 receptor (sCD40) plasma levels were monitored using ELISA. RNA-sequencing was performed with sCD40L-stimulated CC- and TT-genotype HUVEC. Quantitative PCR, Western blot, multiplex-sandwich ELISA array, and immunocytochemistry were used to analyse changes in gene expression in these cells. Results: Homozygosity for the C-allele was associated with a significant 4.3-fold higher odds of developing T2D as compared to individuals homozygous for the T-allele. Inflammation and endothelial-to-mesenchymal transition (EndMT) driving genes were upregulated in CC-genotype but downregulated in TT-genotype HUVEC when exposed to sCD40L. Expression of EndMT markers significantly increased while that of endothelial markers decreased in HUVEC following exposure to hyperglycemia, tumour necrosis factor-α and sCD40L. Conclusions: The -1T > C SNP of the CD40 gene is a risk factor for T2D. Depending on the genotype, it differentially affects gene expression in human cultured EC. CC-genotype HUVEC adopt a pro-inflammatory and intermediate EndMT-like phenotype in a pro-diabetic microenvironment.
Language	English
Publishing date	2023-11-14
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	80061-2
ISSN	1879-1484 ; 0021-9150
ISSN (online)	1879-1484
ISSN	0021-9150
DOI	10.1016/j.atherosclerosis.2023.117386
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Article ; Online: Calciprotein Particles Induce Endothelial Dysfunction by Impairing Endothelial Nitric Oxide Metabolism.

Feenstra, Lian / Kutikhin, Anton G / Shishkova, Daria K / Buikema, Hendrik / Zeper, Lara W / Bourgonje, Arno R / Krenning, Guido / Hillebrands, Jan-Luuk

Arteriosclerosis, thrombosis, and vascular biology

2023 Volume 43, Issue 3, Page(s) 443–455

Abstract: Background: Calciprotein particles (CPPs) are associated with the development of vascular calcifications in chronic kidney disease. The role of endothelial cells (ECs) in this process is unknown. Here, we investigated the interaction of CPPs and ECs, ... ...

Abstract	Background: Calciprotein particles (CPPs) are associated with the development of vascular calcifications in chronic kidney disease. The role of endothelial cells (ECs) in this process is unknown. Here, we investigated the interaction of CPPs and ECs, thereby focusing on endothelial nitric oxide metabolism and oxidative stress. Methods: CPPs were generated in calcium- and phosphate-enriched medium. Human umbilical vein endothelial cells were exposed to different concentrations of CPPs (0-100 µg/mL) for 24 or 72 hours. Ex vivo porcine coronary artery rings were used to measure endothelial cell-dependent vascular smooth muscle cell relaxation after CPP exposure. Serum samples from an early chronic kidney disease cohort (n=245) were analyzed for calcification propensity (measure for CPP formation) and nitrate and nitrite levels (NO Results: CPP exposure for 24 hours reduced eNOS (endothelial nitric oxide synthase) mRNA expression and decreased nitrite production, indicating reduced nitric oxide bioavailability. Also, 24-hour CPP exposure caused increased mitochondria-derived superoxide generation, together with nitrotyrosine protein residue formation. Long-term (72 hours) exposure of human umbilical vein endothelial cells to CPPs induced eNOS uncoupling and decreased eNOS protein expression, indicating further impairment of the nitric oxide pathway. The ex vivo porcine coronary artery model showed a significant reduction in endothelial-dependent vascular smooth muscle cell relaxation after CPP exposure. A negative association was observed between NO Conclusions: CPPs cause endothelial cell dysfunction by impairing nitric oxide metabolism and generating oxidative stress. Our findings provide new evidence for direct effects of CPPs on ECs and pathways involved.
MeSH term(s)	Humans ; Animals ; Swine ; Nitric Oxide/metabolism ; Nitrites/metabolism ; Endothelium/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Vascular Diseases ; Human Umbilical Vein Endothelial Cells/metabolism ; Renal Insufficiency, Chronic/metabolism ; Endothelium, Vascular/metabolism
Chemical Substances	Nitric Oxide (31C4KY9ESH) ; Nitrites ; Nitric Oxide Synthase Type III (EC 1.14.13.39)
Language	English
Publishing date	2023-02-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.122.318420
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Zs.A 1705: Show issues

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Article ; Online: Safety, tolerability and toxicokinetics of the novel mitochondrial drug SUL-138 administered orally to rat and minipig.

Swart, Daniël H / de Haan, Martin / Stevens, Jasper / Henning, Rob H / Adel, Sovan / van der Graaf, Adrianus C / Ulu, Nadir / Touw, Daan J / Krenning, Guido

Toxicology reports

2024 Volume 12, Page(s) 345–355

Abstract: Noncommunicable Chronic Diseases (NCD) are a socioeconomic burden and considered one of the major health challenges for coming decades. Mitochondrial dysfunction has been implicated mechanistically in their pathophysiology. Therefore, targeting ... ...

Abstract	Noncommunicable Chronic Diseases (NCD) are a socioeconomic burden and considered one of the major health challenges for coming decades. Mitochondrial dysfunction has been implicated mechanistically in their pathophysiology. Therefore, targeting mitochondria holds great promise to improve clinical outcomes in NCDs. SUL-138, an orally bioavailable small molecule efficacious from 0.5 mg/kg, improves mitochondrial function during disease in several preclinical animal models. As preparation for a First-in-Human (FIH) trial, SUL-138 was investigated in 30-day GLP repeated dose toxicity studies in rat and minipig, selected based on their comparability with human metabolism, to determine toxicokinetics, potential toxicity and its reversibility. Rats were allocated to either vehicle, 27, 136 or 682 mg/kg SUL-138 dose groups and minipigs were allocated to either vehicle, 16, 82 or 409 mg/kg. Treatment occurred orally for 30 days followed by a recovery period of 14 days. During these studies clinical observations, toxicokinetic, clinical pathology, necropsy and histopathology evaluations were performed. There was significant systemic exposure to SUL-138 and toxicokinetics was characterized by a rapid absorption and elimination. In the rat, toxicokinetics was dose-proportional and AUC
Language	English
Publishing date	2024-03-19
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	2805786-7
ISSN	2214-7500 ; 2214-7500
ISSN (online)	2214-7500
ISSN	2214-7500
DOI	10.1016/j.toxrep.2024.03.009
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Article ; Online: The Endothelium as a Target for Anti-Atherogenic Therapy

Jolien Fledderus / Byambasuren Vanchin / Marianne G. Rots / Guido Krenning

Journal of Personalized Medicine, Vol 11, Iss 2, p

A Focus on the Epigenetic Enzymes EZH2 and SIRT1

2021 Volume 103

Abstract	Endothelial cell inflammatory activation and dysfunction are key events in the pathophysiology of atherosclerosis, and are associated with an elevated risk of cardiovascular events. Yet, therapies specifically targeting the endothelium and atherosclerosis are lacking. Here, we review how endothelial behaviour affects atherogenesis and pose that the endothelium may be an efficacious cellular target for antiatherogenic therapies. We discuss the contribution of endothelial inflammatory activation and dysfunction to atherogenesis and postulate that the dysregulation of specific epigenetic enzymes, EZH2 and SIRT1, aggravate endothelial dysfunction in a pleiotropic fashion. Moreover, we propose that commercially available drugs are available to clinically explore this postulation.
Keywords	endothelial cell ; endothelial dysfunction ; atherosclerosis ; arteriosclerosis ; epigenetics ; EZH2 ; Medicine ; R
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Calciprotein Particles: Balancing Mineral Homeostasis and Vascular Pathology.

Kutikhin, Anton G / Feenstra, Lian / Kostyunin, Alexander E / Yuzhalin, Arseniy E / Hillebrands, Jan-Luuk / Krenning, Guido

Arteriosclerosis, thrombosis, and vascular biology

2021 Volume 41, Issue 5, Page(s) 1607–1624

Abstract: Figure: see text]. ...

Abstract	[Figure: see text].
MeSH term(s)	Animals ; Arteries/drug effects ; Arteries/metabolism ; Arteries/pathology ; Atherosclerosis/blood ; Atherosclerosis/etiology ; Atherosclerosis/pathology ; Atherosclerosis/prevention & control ; Biomarkers/blood ; Calcium/blood ; Calcium Chelating Agents/therapeutic use ; Crystallization ; Homeostasis ; Humans ; Hypercalcemia/blood ; Hypercalcemia/complications ; Hypercalcemia/drug therapy ; Hyperphosphatemia/blood ; Hyperphosphatemia/complications ; Hyperphosphatemia/drug therapy ; Phosphates/blood ; Risk Factors ; Vascular Calcification/blood ; Vascular Calcification/etiology ; Vascular Calcification/pathology ; Vascular Calcification/prevention & control
Chemical Substances	Biomarkers ; Calcium Chelating Agents ; Phosphates ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2021-03-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.120.315697
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Zs.A 1705: Show issues

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Article ; Conference proceedings: Impact of a CD40 gene single-nucleotide polymorphism on the development of endothelial dysfunction under diabetic conditions

Joshi, Pooja / Mohr, Franziska / Kopf, Stefan / Krenning, Guido / Hecker, Markus / Wagner, Andreas

Diabetologie und Stoffwechsel

2022 Volume 17, Issue S 01

Event/congress	Diabetes Kongress 2022 - 56. Jahrestagung der DDG, CityCube Berlin, 2022-05-25
Language	English
Publishing date	2022-05-01
Publisher	Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article ; Conference proceedings
ZDB-ID	2222993-0
ISSN	1861-9010 ; 1861-9002
ISSN (online)	1861-9010
ISSN	1861-9002
DOI	10.1055/s-0042-1746351
Database	Thieme publisher's database

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Zs.A 6479: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.A 6479/X: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)

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Article: Micromanaging cardiac regeneration: Targeted delivery of microRNAs for cardiac repair and regeneration.

Kamps, Jan Aam / Krenning, Guido

World journal of cardiology

2016 Volume 8, Issue 2, Page(s) 163–179

Abstract: The loss of cardiomyocytes during injury and disease can result in heart failure and sudden death, while the adult heart has a limited capacity for endogenous regeneration and repair. Current stem cell-based regenerative medicine approaches modestly ... ...

Abstract	The loss of cardiomyocytes during injury and disease can result in heart failure and sudden death, while the adult heart has a limited capacity for endogenous regeneration and repair. Current stem cell-based regenerative medicine approaches modestly improve cardiomyocyte survival, but offer neglectable cardiomyogenesis. This has prompted the need for methodological developments that crease de novo cardiomyocytes. Current insights in cardiac development on the processes and regulatory mechanisms in embryonic cardiomyocyte differentiation provide a basis to therapeutically induce these pathways to generate new cardiomyocytes. Here, we discuss the current knowledge on embryonic cardiomyocyte differentiation and the implementation of this knowledge in state-of-the-art protocols to the direct reprogramming of cardiac fibroblasts into de novo cardiomyocytes in vitro and in vivo with an emphasis on microRNA-mediated reprogramming. Additionally, we discuss current advances on state-of-the-art targeted drug delivery systems that can be employed to deliver these microRNAs to the damaged cardiac tissue. Together, the advances in our understanding of cardiac development, recent advances in microRNA-based therapeutics, and innovative drug delivery systems, highlight exciting opportunities for effective therapies for myocardial infarction and heart failure.
Language	English
Publishing date	2016-03-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2573665-6
ISSN	1949-8462
ISSN	1949-8462
DOI	10.4330/wjc.v8.i2.163
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