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Article ; Online: The Kidney: An Organ in the Front Line of Oxidative Stress-Associated Pathologies.

Gorin, Yves

2016 Volume 25, Issue 12, Page(s) 639–641

Abstract: Both acute kidney injury (AKI) and chronic kidney disease (CKD) are major causes of renal failure in humans and are associated with high incidences of morbidity and mortality rates. AKI and CKD are closely interconnected, and fueled by the obesity and ... ...

Abstract	Both acute kidney injury (AKI) and chronic kidney disease (CKD) are major causes of renal failure in humans and are associated with high incidences of morbidity and mortality rates. AKI and CKD are closely interconnected, and fueled by the obesity and diabetes epidemic, their prevalence is alarmingly increasing to the point that it currently represents a major heath issue worldwide. The kidney is an organ that is particularly sensitive to redox imbalance, resulting in excessive production of reactive oxygen species. Oxidative stress is viewed as a critical pathogenic factor implicated in the initiation, development, and progression of most renal diseases. This Forum discusses the redox-dependent factors and mechanisms accounting for the perturbation of renal function and circulation in the context of the major kidney pathologies linked to hypertension, diabetes, and cancer. Antioxid. Redox Signal. 25, 639-641.
MeSH term(s)	Acute Kidney Injury/etiology ; Acute Kidney Injury/metabolism ; Acute Kidney Injury/pathology ; Diabetes Complications ; Disease Progression ; Humans ; Hypertension/metabolism ; Hypertension/pathology ; Kidney/metabolism ; Kidney/pathology ; Kidney Failure, Chronic/metabolism ; Kidney Failure, Chronic/pathology ; Obesity/complications ; Oxidation-Reduction ; Reactive Oxygen Species/metabolism ; Renal Insufficiency, Chronic/etiology ; Renal Insufficiency, Chronic/metabolism ; Renal Insufficiency, Chronic/pathology
Chemical Substances	Reactive Oxygen Species
Language	English
Publishing date	2016-08-01
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ars.2016.6804
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Article ; Online: Nox4 as a potential therapeutic target for treatment of uremic toxicity associated to chronic kidney disease.

Gorin, Yves

Kidney international

2012 Volume 83, Issue 4, Page(s) 541–543

Abstract: Watanabe et al. report that Nox4 NADPH oxidase catalytic moiety and the subunit p22(phox) mediate the increase in oxidative stress and human tubular epithelial cell injury induced by p-cresyl sulfate, a protein-bound uremic toxin. These findings could be ...

Abstract	Watanabe et al. report that Nox4 NADPH oxidase catalytic moiety and the subunit p22(phox) mediate the increase in oxidative stress and human tubular epithelial cell injury induced by p-cresyl sulfate, a protein-bound uremic toxin. These findings could be instrumental for the design of novel therapeutic intervention utilizing small-molecule inhibitors specifically targeting Nox oxidases to prevent or slow down the progression of chronic kidney disease and the associated disorders due to uremic toxicity.
MeSH term(s)	Animals ; Cresols/toxicity ; Epithelial Cells/drug effects ; Humans ; Kidney Tubules, Proximal/drug effects ; Male ; NADPH Oxidases/metabolism ; Oxidative Stress/drug effects ; Renal Insufficiency, Chronic/chemically induced ; Sulfuric Acid Esters/toxicity
Chemical Substances	Cresols ; Sulfuric Acid Esters ; 4-cresol sulfate (56M34ZQY1S) ; NADPH Oxidases (EC 1.6.3.-)
Language	English
Publishing date	2012-10-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1038/ki.2012.434
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Article ; Online: Circular Geometry in Molecular Stream Separation to Facilitate Nonorthogonal Field-to-Flow Orientation.

Kochmann, Sven / Ivanov, Nikita A / Le Blanc, J C Yves / Gorin, Boris I / Krylov, Sergey N

Analytical chemistry

2022 Volume 94, Issue 27, Page(s) 9519–9524

Abstract: Molecular stream separation (MSS) is a promising complement for continuous-flow synthesis. MSS is driven by forces exerted on molecules by a field applied at an angle to the stream-carrying flow. MSS has only been performed with a 90° field-to-flow angle ...

Abstract	Molecular stream separation (MSS) is a promising complement for continuous-flow synthesis. MSS is driven by forces exerted on molecules by a field applied at an angle to the stream-carrying flow. MSS has only been performed with a 90° field-to-flow angle because of a rectangular geometry of canonic MSS; the second-order rotational symmetry of a rectangle prevents any other angle. Here, we propose a noncanonic circular geometry for MSS, which better aligns with the polar nature of MSS and allows changing the field-to-flow. We conducted in silico and experimental studies of circular geometry for continuous-flow electrophoresis (CFE, an MSS method). We proved two advantages of circular CFE over its rectangular counterpart. First, circular CFE can support better flow and electric-field uniformity than rectangular CFE. Second, the nonorthogonal field-to-flow orientation, achievable in circular CFE, can result in a higher stream resolution than the orthogonal one. Considering that circular CFE devices are not more complex in fabrication than rectangular ones, we foresee that circular CFE will serve as a new standard and a testbed for the investigation and creation of new CFE modalities.
MeSH term(s)	Electricity ; Electrophoresis/methods ; Mathematics ; Rivers
Language	English
Publishing date	2022-06-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.2c01829
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Article ; Online: Implantation of engineered human microvasculature to study human infectious diseases in mouse models.

Schönherr-Hellec, Sophia / Chatzopoulou, Eirini / Barnier, Jean-Philippe / Atlas, Yoann / Dupichaud, Sébastien / Guilbert, Thomas / Dupraz, Yves / Meyer, Julie / Chaussain, Catherine / Gorin, Caroline / Nassif, Xavier / Germain, Stephane / Muller, Laurent / Coureuil, Mathieu

iScience

2023 Volume 26, Issue 4, Page(s) 106286

Abstract: Animal models for studying human pathogens are crucially lacking. We describe the implantation in mice of engineered human mature microvasculature consisting of endothelial and perivascular cells embedded in collagen hydrogel that allows investigation of ...

Abstract	Animal models for studying human pathogens are crucially lacking. We describe the implantation in mice of engineered human mature microvasculature consisting of endothelial and perivascular cells embedded in collagen hydrogel that allows investigation of pathogen interactions with the endothelium, including
Language	English
Publishing date	2023-02-27
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.106286
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Article ; Online: Transient Incomplete Separation of Species with Close Diffusivity to Study the Stability of Affinity Complexes.

Wang, Tong Ye / Rukundo, Jean-Luc / Le, An T H / Ivanov, Nikita A / Le Blanc, J C Yves / Gorin, Boris I / Krylov, Sergey N

Analytical chemistry

2022 Volume 94, Issue 44, Page(s) 15415–15422

Abstract: Large molecules can be generically separated from small ones, though partially and temporarily, in a pressure-driven flow inside a capillary. This transient incomplete separation has been only applied to species with diffusion coefficients different by ... ...

Abstract	Large molecules can be generically separated from small ones, though partially and temporarily, in a pressure-driven flow inside a capillary. This transient incomplete separation has been only applied to species with diffusion coefficients different by at least an order of magnitude. Here, we demonstrate, for the first time, the analytical utility of transient incomplete separation for species with close diffusion coefficients. First, we prove
MeSH term(s)	Electrophoresis, Capillary/methods ; Computer Simulation ; Protein Binding ; Oligonucleotides/chemistry ; Entropy
Chemical Substances	Oligonucleotides
Language	English
Publishing date	2022-10-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.2c03313
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Article ; Online: Template Instrumentation for "Accurate Constant via Transient Incomplete Separation".

Rukundo, Jean-Luc / Kochmann, Sven / Wang, Tong Ye / Ivanov, Nikita A / Le Blanc, J C Yves / Gorin, Boris I / Krylov, Sergey N

Analytical chemistry

2021 Volume 93, Issue 34, Page(s) 11654–11659

Abstract: Accurate Constant via Transient Incomplete Separation (ACTIS) is a new method for finding the equilibrium dissociation ... ...

Abstract	Accurate Constant via Transient Incomplete Separation (ACTIS) is a new method for finding the equilibrium dissociation constant
MeSH term(s)	Entropy
Language	English
Publishing date	2021-08-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.1c02007
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Article ; Online: Upstream regulators and downstream effectors of NADPH oxidases as novel therapeutic targets for diabetic kidney disease.

Gorin, Yves / Wauquier, Fabien

Molecules and cells

2015 Volume 38, Issue 4, Page(s) 285–296

Abstract: Oxidative stress has been linked to the pathogenesis of diabetic nephropathy, the complication of diabetes in the kidney. NADPH oxidases of the Nox family, and in particular the homologue Nox4, are a major source of reactive oxygen species in the ... ...

Abstract	Oxidative stress has been linked to the pathogenesis of diabetic nephropathy, the complication of diabetes in the kidney. NADPH oxidases of the Nox family, and in particular the homologue Nox4, are a major source of reactive oxygen species in the diabetic kidney and are critical mediators of redox signaling in glomerular and tubulointerstitial cells exposed to the diabetic milieu. Here, we present an overview of the current knowledge related to the understanding of the role of Nox enzymes in the processes that control mesangial cell, podocyte and tubulointerstitial cell injury induced by hyperglycemia and other predominant factors enhanced in the diabetic milieu, including the renin-angiotensin system and transforming growth factor-β. The nature of the upstream modulators of Nox enzymes as well as the downstream targets of the Nox NADPH oxidases implicated in the propagation of the redox processes that alter renal biology in diabetes will be highlighted.
MeSH term(s)	Animals ; Diabetic Nephropathies/drug therapy ; Diabetic Nephropathies/enzymology ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/pathology ; Humans ; Molecular Targeted Therapy ; NADPH Oxidases/metabolism ; Oxidative Stress ; Signal Transduction
Chemical Substances	NADPH Oxidases (EC 1.6.3.-)
Language	English
Publishing date	2015-03-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1148964-9
ISSN	0219-1032 ; 1016-8478
ISSN (online)	0219-1032
ISSN	1016-8478
DOI	10.14348/molcells.2015.0010
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Article ; Online: Implantation of engineered human microvasculature to study human infectious diseases in mouse models

Sophia Schönherr-Hellec / Eirini Chatzopoulou / Jean-Philippe Barnier / Yoann Atlas / Sébastien Dupichaud / Thomas Guilbert / Yves Dupraz / Julie Meyer / Catherine Chaussain / Caroline Gorin / Xavier Nassif / Stephane Germain / Laurent Muller / Mathieu Coureuil

iScience, Vol 26, Iss 4, Pp 106286- (2023)

2023

Abstract: Summary: Animal models for studying human pathogens are crucially lacking. We describe the implantation in mice of engineered human mature microvasculature consisting of endothelial and perivascular cells embedded in collagen hydrogel that allows ... ...

Abstract	Summary: Animal models for studying human pathogens are crucially lacking. We describe the implantation in mice of engineered human mature microvasculature consisting of endothelial and perivascular cells embedded in collagen hydrogel that allows investigation of pathogen interactions with the endothelium, including in vivo functional studies. Using Neisseria meningitidis as a paradigm of human-restricted infection, we demonstrated the strength and opportunities associated with the use of this approach.
Keywords	Biological sciences ; Microbiology ; Bioengineering ; Cell biology ; Science ; Q
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Circular Geometry in Molecular Stream Separation to Facilitate Nonorthogonal Field-to-Flow Orientation

Kochmann, Sven / Ivanov, Nikita A. / Le Blanc, J. C. Yves / Gorin, Boris I. / Krylov, Sergey N.

Analytical chemistry. 2022 June 29, v. 94, no. 27

2022

Abstract	Molecular stream separation (MSS) is a promising complement for continuous-flow synthesis. MSS is driven by forces exerted on molecules by a field applied at an angle to the stream-carrying flow. MSS has only been performed with a 90° field-to-flow angle because of a rectangular geometry of canonic MSS; the second-order rotational symmetry of a rectangle prevents any other angle. Here, we propose a noncanonic circular geometry for MSS, which better aligns with the polar nature of MSS and allows changing the field-to-flow. We conducted in silico and experimental studies of circular geometry for continuous-flow electrophoresis (CFE, an MSS method). We proved two advantages of circular CFE over its rectangular counterpart. First, circular CFE can support better flow and electric-field uniformity than rectangular CFE. Second, the nonorthogonal field-to-flow orientation, achievable in circular CFE, can result in a higher stream resolution than the orthogonal one. Considering that circular CFE devices are not more complex in fabrication than rectangular ones, we foresee that circular CFE will serve as a new standard and a testbed for the investigation and creation of new CFE modalities.
Keywords	analytical chemistry ; computer simulation ; electric field ; electrophoresis ; geometry ; streams
Language	English
Dates of publication	2022-0629
Size	p. 9519-9524.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.2c01829
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Interplay between RNA-binding protein HuR and Nox4 as a novel therapeutic target in diabetic kidney disease.

Shi, Qian / Lee, Doug-Yoon / Féliers, Denis / Abboud, Hanna E / Bhat, Manzoor A / Gorin, Yves

Molecular metabolism

2020 Volume 36, Page(s) 100968

Abstract: Objective: Glomerular injury is a prominent pathological feature of diabetic kidney disease (DKD). Constitutively active NADPH oxidase 4 (Nox4) is a major source of reactive oxygen species that mediates hyperglycemia-induced mesangial cell (MC) fibrotic ...

Abstract	Objective: Glomerular injury is a prominent pathological feature of diabetic kidney disease (DKD). Constitutively active NADPH oxidase 4 (Nox4) is a major source of reactive oxygen species that mediates hyperglycemia-induced mesangial cell (MC) fibrotic injury. However, the mechanism that Nox4 utilizes to achieve its biological outcome remains elusive, and the signaling pathways that regulate this isoform oxidase are not well understood. Here, our goal is to study the detailed mechanism by which NAPDH oxidase 4 (Nox4) is post-transcriptionally regulated in MC during diabetic pathology. Methods: We studied the protein expression of HuR, Nox4 and matrix proteins by western blotting, while we assessed the mRNA stability of Nox4 by RT-PCR and polysomal assay, examined in vitro cultured glomerular mesangial cells treated by high glucose (HG) and diabetic animal induced by STZ. The binding assay between HuR and the Nox4 promoter was done by immuno-precipiating with HuR antibody and detecting the presence of Nox4 mRNA, or by pull-down by using biotinlyated labeled Nox4 promoter RNA and detecting the presence of the HuR protein. The binding was also confirmed in MCs where Nox4 promoter-containing luciferage constructs were transfected. ROS levels were measured with DHE/DCF dyes in cells, or lucigenin chemiluminescence for Nox enzymatic levels, or HPLC assay for superoxide. HuR protein was inhibited by antisense oligo that utilized osmotic pumps for continuous delivery in animal models. The H1bAc1 ratio was measured by an ELISA kit for mice. Results: We demonstrate that in MCs, high glucose (HG) elicits a rapid upregulation of Nox4 protein via translational mechanisms. Nox4 mRNA 3' untranslated region (3'-UTR) contains numerous AU-rich elements (AREs) that are potential binding sites for the RNA-binding protein human antigen R (HuR). We show that HG promotes HuR activation/expression and that HuR is required for HG-induced Nox4 protein expression/mRNA translation, ROS generation, and subsequent MC fibrotic injury. Through a series of invitro RNA-binding assays, we demonstrate that HuR acts via binding to AREs in Nox4 3'-UTR in response to HG. The invivo relevance of these observations is confirmed by the findings that increased Nox4 is accompanied by the binding of HuR to Nox4 mRNA in kidneys from type 1 diabetic animals, and further suppressing HuR expression showed a reno-protective role in a type 1 diabetic mouse model via reducing MC injury, along with the improvement of hyperglycemia and renal function. Conclusions: We established for the first time that HuR-mediated translational regulation of Nox4 contributes to the pathogenesis of fibrosis of the glomerular microvascular bed. Thus therapeutic interventions affecting the interplay between Nox4 and HuR could be exploited as valuable tools in designing treatments for DKD.
MeSH term(s)	Animals ; Cells, Cultured ; Diabetes Mellitus/metabolism ; Diabetes Mellitus, Experimental/metabolism ; Diabetic Nephropathies/genetics ; Diabetic Nephropathies/therapy ; ELAV-Like Protein 1/genetics ; ELAV-Like Protein 1/metabolism ; Glucose/metabolism ; Humans ; Hyperglycemia/metabolism ; Kidney/pathology ; Male ; Mice ; Mice, Inbred C57BL ; NADPH Oxidase 4/genetics ; NADPH Oxidase 4/metabolism ; RNA-Binding Proteins/metabolism ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects
Chemical Substances	ELAV-Like Protein 1 ; ELAVL1 protein, human ; Elavl1 protein, mouse ; RNA-Binding Proteins ; Reactive Oxygen Species ; NADPH Oxidase 4 (EC 1.6.3.-) ; NOX4 protein, human (EC 1.6.3.-) ; Nox4 protein, mouse (EC 1.6.3.-) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2020-02-28
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2708735-9
ISSN	2212-8778 ; 2212-8778
ISSN (online)	2212-8778
ISSN	2212-8778
DOI	10.1016/j.molmet.2020.02.011
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