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Article ; Online: CRISPR-AsCas12a Efficiently Corrects a

Torriano, Simona / Baulier, Edouard / Garcia Diaz, Alejandro / Corneo, Barbara / Farber, Debora B

2022 Volume 5, Issue 3, Page(s) 457–471

Abstract: Mutations in ... ...

Abstract	Mutations in the
MeSH term(s)	Albinism, Ocular/genetics ; Albinism, Ocular/metabolism ; Albinism, Ocular/pathology ; CRISPR-Cas Systems/genetics ; Eye Proteins/genetics ; Eye Proteins/metabolism ; Gene Editing ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Mutation
Chemical Substances	Eye Proteins ; GPR143 protein, human ; Membrane Glycoproteins
Language	English
Publishing date	2022-06-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3017891-5
ISSN	2573-1602 ; 2573-1599
ISSN (online)	2573-1602
ISSN	2573-1599
DOI	10.1089/crispr.2021.0110
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Article ; Online: The bacterial lysate OM-85 engages Toll-like receptors 2 and 4 triggering an immunomodulatory gene signature in human myeloid cells.

Khameneh, Hanif J / Bolis, Marco / Ventura, Pedro M O / Cassanmagnago, Giada A / Fischer, Berenice A / Zenobi, Alessandro / Guerra, Jessica / Buzzago, Irene / Bernasconi, Maurizio / Zaman, Guido J R / Rinaldi, Andrea / Moro, Simone G / Sallusto, Federica / Baulier, Edouard / Pasquali, Christian / Guarda, Greta

Mucosal immunology

2024

Abstract: OM-85 is a bacterial lysate used in clinical practice to reduce duration and frequency of recurrent respiratory tract infections. Whereas knowledge of its regulatory effects in vivo has substantially advanced, the mechanisms of OM-85 sensing remain ... ...

Abstract	OM-85 is a bacterial lysate used in clinical practice to reduce duration and frequency of recurrent respiratory tract infections. Whereas knowledge of its regulatory effects in vivo has substantially advanced, the mechanisms of OM-85 sensing remain inadequately addressed. Here, we show that the immune response to OM-85 in the mouse is largely mediated by myeloid immune cells through Toll-like receptor (TLR) 4 in vitro and in vivo. Instead, in human immune cells, TLR2 and TLR4 orchestrate the response to OM-85, which binds to both receptors as shown by surface plasmon resonance assay. Ribonucleic acid-sequencing analyses of human monocyte-derived dendritic cells reveal that OM-85 triggers a pro-inflammatory signature and a unique gene set, which is not induced by canonical agonists of TLR2 or TLR4 and comprises tolerogenic genes. A largely overlapping TLR2/4-dependent gene signature was observed in individual subsets of primary human airway myeloid cells, highlighting the robust effects of OM-85. Collectively, our results suggest caution should be taken when relating murine studies on bacterial lysates to humans. Furthermore, our data shed light on how a standardized bacterial lysate shapes the response through TLR2 and TLR4, which are crucial for immune response, trained immunity, and tolerance.
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2411370-0
ISSN	1935-3456 ; 1933-0219
ISSN (online)	1935-3456
ISSN	1933-0219
DOI	10.1016/j.mucimm.2024.02.010
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Article ; Online: Generation of a human Ocular Albinism type 1 iPSC line, SEIi001-A, with a mutation in GPR143.

Baulier, Edouard / Garcia Diaz, Alejandro / Corneo, Barbara / Farber, Debora B

Stem cell research

2018 Volume 33, Page(s) 274–277

Abstract: Ocular albinism type 1 is a genetic eye disease caused by mutations in the GPR143 gene. Little is known about the molecular pathways involved in this disease and no therapeutic candidate has been identified as yet. Here we report the generation of an ... ...

Abstract	Ocular albinism type 1 is a genetic eye disease caused by mutations in the GPR143 gene. Little is known about the molecular pathways involved in this disease and no therapeutic candidate has been identified as yet. Here we report the generation of an iPSC line from the skin fibroblasts of a patient with a mutation in the GPR143 gene using Sendai Virus vectors. This new iPSC line will allow a better understanding of the Ocular Albinism type 1 disease and to screen for potential therapeutic candidates.
MeSH term(s)	Adult ; Albinism, Ocular/genetics ; Eye Proteins/genetics ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Male ; Membrane Glycoproteins/genetics ; Mutation
Chemical Substances	Eye Proteins ; GPR143 protein, human ; Membrane Glycoproteins
Language	English
Publishing date	2018-11-28
Publishing country	England
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1876-7753
ISSN (online)	1876-7753
DOI	10.1016/j.scr.2018.11.016
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Generation of a human Ocular Albinism type 1 iPSC line, SEIi001-A, with a mutation in GPR143

Edouard Baulier / Alejandro Garcia Diaz / Barbara Corneo / Debora B. Farber

Stem Cell Research, Vol 33, Iss , Pp 274-

2018 Volume 277

Abstract	Ocular albinism type 1 is a genetic eye disease caused by mutations in the GPR143 gene. Little is known about the molecular pathways involved in this disease and no therapeutic candidate has been identified as yet. Here we report the generation of an iPSC line from the skin fibroblasts of a patient with a mutation in the GPR143 gene using Sendai Virus vectors. This new iPSC line will allow a better understanding of the Ocular Albinism type 1 disease and to screen for potential therapeutic candidates.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2018-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hypercholesterolemia-induced increase in plasma oxidized LDL abrogated pro angiogenic response in kidney grafts.

Kerforne, Thomas / Favreau, Frédéric / Khalifeh, Tackwa / Maiga, Souleymane / Allain, Geraldine / Thierry, Antoine / Dierick, Manuel / Baulier, Edouard / Steichen, Clara / Hauet, Thierry

Journal of translational medicine

2019 Volume 17, Issue 1, Page(s) 26

Abstract: Background: Renal transplantation is increasingly associated with the presence of comorbidity factors such as dyslipidemia which could influence the graft outcome. We hypothesized that hypercholesterolemia could affect vascular repair processes and ... ...

Abstract	Background: Renal transplantation is increasingly associated with the presence of comorbidity factors such as dyslipidemia which could influence the graft outcome. We hypothesized that hypercholesterolemia could affect vascular repair processes and promote post-transplant renal vascular remodeling through the over-expression of the anti-angiogenic thrombospondin-1 interacting with vascular endothelial growth factor-A levels. Methods: We tested this hypothesis in vitro, in vivo and in a human cohort using (1) endothelial cells; (2) kidney auto-transplanted pig subjected (n = 5) or not (n = 6) to a diet enriched in cholesterol and (3) a renal transplanted patient cohort (16 patients). Results: Cells exposed to oxidized LDL showed reduced proliferation and an increased expression of thrombospondin-1. In pigs, 3 months after transplantation of kidney grafts, we observed a deregulation of the hypoxia inducible factor 1a-vascular endothelial growth factor-A axis induced in cholesterol-enriched diet animals concomitant with an overexpression of thrombospondin-1 and a decrease in cortical microvessel density promoting vascular remodeling. In patients, hypercholesterolemia was associated with decreased vascular endothelial growth factor-A plasma levels during early follow up after renal transplantation and increased chronic graft dysfunction. Conclusions: These results support a potential mechanism through which a high fat-diet impedes vascular repair in kidney graft and suggest the value of controlling cholesterolemia in recipient even at the early stage of renal transplantation.
MeSH term(s)	Adult ; Animals ; Aorta/pathology ; Biomarkers/metabolism ; Cell Proliferation/drug effects ; Diet, High-Fat ; Endothelial Cells/metabolism ; Female ; Humans ; Hypercholesterolemia/blood ; Hypercholesterolemia/physiopathology ; Kidney Function Tests ; Kidney Transplantation ; Lipoproteins, LDL/blood ; Macrophages/pathology ; Male ; Middle Aged ; Neovascularization, Physiologic ; Swine ; Thrombospondins/metabolism ; Vascular Endothelial Growth Factor A/blood ; Vascular Remodeling
Chemical Substances	Biomarkers ; Lipoproteins, LDL ; Thrombospondins ; Vascular Endothelial Growth Factor A ; oxidized low density lipoprotein
Language	English
Publishing date	2019-01-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1479-5876
ISSN (online)	1479-5876
DOI	10.1186/s12967-018-1764-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Human embryonic stem cells extracellular vesicles and their effects on immortalized human retinal Müller cells.

Peng, Yingqian / Baulier, Edouard / Ke, Yifeng / Young, Alejandra / Ahmedli, Novruz B / Schwartz, Steven D / Farber, Debora B

PloS one

2018 Volume 13, Issue 3, Page(s) e0194004

Abstract: Extracellular vesicles (EVs) released by virtually every cell of all organisms are involved in processes of intercellular communication through the delivery of their functional mRNAs, proteins and bioactive lipids. We previously demonstrated that mouse ... ...

Abstract	Extracellular vesicles (EVs) released by virtually every cell of all organisms are involved in processes of intercellular communication through the delivery of their functional mRNAs, proteins and bioactive lipids. We previously demonstrated that mouse embryonic stem cell-released EVs (mESEVs) are able to transfer their content to different target retinal cells, inducing morphological and biochemical changes in them. The main objective of this paper is to characterize EVs derived from human embryonic stem cells (hESEVs) and investigate the effects that they have on cultured retinal glial, progenitor Müller cells, which are known to give rise to retinal neurons under specific conditions. This would allow us to establish if hESEVs have a pro-regenerative potential not yet described that could be used in the future for treatment of human retinal degenerative diseases. Initially, we showed that hESEVs are heterogeneous in size, contain mRNAs and proteins involved in the induction and maintenance of stem cell pluripotency and can be internalized by cultured Müller cells. After a single exposure to hESEVs these cells display changes in their gene expression profile, and with multiple exposures they de-differentiate and trans-differentiate into retinal neuronal precursors. hESEVs were then fractionated into microvesicles (MVs) and exosomes (EXOs), which were characterized by size, specific surface proteins and biochemical/molecular components. We demonstrate that despite the similar internalization of non-fractionated hESEVs, MVs and EXOs by Müller progenitor cells, in vitro, only the release of MVs' cargo into the cells' cytoplasm induces specific changes in their levels of pluripotency mRNAs and early retinal proteins. EXOs do not produce any detectable effect. Thus, we conclude that MVs and MVs-containing hESEVs are promising agents that possibly could promote the regeneration of diseased or damaged retinas in vivo through inducing glial Müller cells to become replacement neurons.
MeSH term(s)	Cell-Derived Microparticles/metabolism ; Cell-Derived Microparticles/physiology ; Cells, Cultured ; Ependymoglial Cells/metabolism ; Ependymoglial Cells/physiology ; Exosomes/metabolism ; Exosomes/physiology ; Extracellular Vesicles/metabolism ; Extracellular Vesicles/physiology ; HEK293 Cells ; Human Embryonic Stem Cells/metabolism ; Human Embryonic Stem Cells/physiology ; Humans ; Neuroglia/metabolism ; Neuroglia/physiology ; Neurons/metabolism ; Neurons/physiology ; Pluripotent Stem Cells/metabolism ; Pluripotent Stem Cells/physiology ; RNA, Messenger/metabolism ; Regeneration/physiology ; Retina/metabolism ; Retina/physiology ; Transcriptome/physiology
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2018-03-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0194004
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Article ; Online: Hypercholesterolemia-induced increase in plasma oxidized LDL abrogated pro angiogenic response in kidney grafts

Thomas Kerforne / Frédéric Favreau / Tackwa Khalifeh / Souleymane Maiga / Geraldine Allain / Antoine Thierry / Manuel Dierick / Edouard Baulier / Clara Steichen / Thierry Hauet

Journal of Translational Medicine, Vol 17, Iss 1, Pp 1-

2019 Volume 14

Abstract: Abstract Background Renal transplantation is increasingly associated with the presence of comorbidity factors such as dyslipidemia which could influence the graft outcome. We hypothesized that hypercholesterolemia could affect vascular repair processes ... ...

Abstract	Abstract Background Renal transplantation is increasingly associated with the presence of comorbidity factors such as dyslipidemia which could influence the graft outcome. We hypothesized that hypercholesterolemia could affect vascular repair processes and promote post-transplant renal vascular remodeling through the over-expression of the anti-angiogenic thrombospondin-1 interacting with vascular endothelial growth factor-A levels. Methods We tested this hypothesis in vitro, in vivo and in a human cohort using (1) endothelial cells; (2) kidney auto-transplanted pig subjected (n = 5) or not (n = 6) to a diet enriched in cholesterol and (3) a renal transplanted patient cohort (16 patients). Results Cells exposed to oxidized LDL showed reduced proliferation and an increased expression of thrombospondin-1. In pigs, 3 months after transplantation of kidney grafts, we observed a deregulation of the hypoxia inducible factor 1a—vascular endothelial growth factor-A axis induced in cholesterol-enriched diet animals concomitant with an overexpression of thrombospondin-1 and a decrease in cortical microvessel density promoting vascular remodeling. In patients, hypercholesterolemia was associated with decreased vascular endothelial growth factor-A plasma levels during early follow up after renal transplantation and increased chronic graft dysfunction. Conclusions These results support a potential mechanism through which a high fat-diet impedes vascular repair in kidney graft and suggest the value of controlling cholesterolemia in recipient even at the early stage of renal transplantation.
Keywords	Oxidized LDL ; Kidney transplantation ; Vascular remodeling ; Medicine ; R
Subject code	616 ; 610
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Vectisol Formulation Enhances Solubility of Resveratrol and Brings Its Benefits to Kidney Transplantation in a Preclinical Porcine Model.

Soussi, David / Danion, Jérôme / Baulier, Edouard / Favreau, Frédéric / Sauvageon, Ysé / Bossard, Valentin / Matillon, Xavier / Turpin, Frédéric / Belgsir, El Mustapha / Thuillier, Raphaël / Hauet, Thierry

International journal of molecular sciences

2019 Volume 20, Issue 9

Abstract: Current organ shortages have led centers to extend the acceptance criteria for organs, increasing the risk for adverse outcomes. Current preservation protocols have not been adapted so as to efficiently protect these organs. Herein, we target oxidative ... ...

Abstract	Current organ shortages have led centers to extend the acceptance criteria for organs, increasing the risk for adverse outcomes. Current preservation protocols have not been adapted so as to efficiently protect these organs. Herein, we target oxidative stress, the key mechanism of ischemia reperfusion injury. Vectisol
MeSH term(s)	Animals ; Antioxidants/administration & dosage ; Antioxidants/chemistry ; Cyclodextrins/administration & dosage ; Cyclodextrins/chemistry ; Disease Models, Animal ; Drug Compounding ; Humans ; Kidney/drug effects ; Kidney/physiopathology ; Kidney Transplantation/adverse effects ; Organ Preservation/methods ; Oxidative Stress/drug effects ; Reperfusion Injury/drug therapy ; Reperfusion Injury/physiopathology ; Resveratrol/administration & dosage ; Resveratrol/chemistry ; Solubility ; Swine ; Transplantation, Autologous
Chemical Substances	Antioxidants ; Cyclodextrins ; Resveratrol (Q369O8926L)
Language	English
Publishing date	2019-05-08
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/ijms20092268
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Article ; Online: Human embryonic stem cells extracellular vesicles and their effects on immortalized human retinal Müller cells.

Yingqian Peng / Edouard Baulier / Yifeng Ke / Alejandra Young / Novruz B Ahmedli / Steven D Schwartz / Debora B Farber

PLoS ONE, Vol 13, Iss 3, p e

2018 Volume 0194004

Abstract	Extracellular vesicles (EVs) released by virtually every cell of all organisms are involved in processes of intercellular communication through the delivery of their functional mRNAs, proteins and bioactive lipids. We previously demonstrated that mouse embryonic stem cell-released EVs (mESEVs) are able to transfer their content to different target retinal cells, inducing morphological and biochemical changes in them. The main objective of this paper is to characterize EVs derived from human embryonic stem cells (hESEVs) and investigate the effects that they have on cultured retinal glial, progenitor Müller cells, which are known to give rise to retinal neurons under specific conditions. This would allow us to establish if hESEVs have a pro-regenerative potential not yet described that could be used in the future for treatment of human retinal degenerative diseases. Initially, we showed that hESEVs are heterogeneous in size, contain mRNAs and proteins involved in the induction and maintenance of stem cell pluripotency and can be internalized by cultured Müller cells. After a single exposure to hESEVs these cells display changes in their gene expression profile, and with multiple exposures they de-differentiate and trans-differentiate into retinal neuronal precursors. hESEVs were then fractionated into microvesicles (MVs) and exosomes (EXOs), which were characterized by size, specific surface proteins and biochemical/molecular components. We demonstrate that despite the similar internalization of non-fractionated hESEVs, MVs and EXOs by Müller progenitor cells, in vitro, only the release of MVs' cargo into the cells' cytoplasm induces specific changes in their levels of pluripotency mRNAs and early retinal proteins. EXOs do not produce any detectable effect. Thus, we conclude that MVs and MVs-containing hESEVs are promising agents that possibly could promote the regeneration of diseased or damaged retinas in vivo through inducing glial Müller cells to become replacement neurons.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Vectisol Formulation Enhances Solubility of Resveratrol and Brings Its Benefits to Kidney Transplantation in a Preclinical Porcine Model

David Soussi / Jérôme Danion / Edouard Baulier / Frédéric Favreau / Ysé Sauvageon / Valentin Bossard / Xavier Matillon / Frédéric Turpin / El Mustapha Belgsir / Raphaël Thuillier / Thierry Hauet

International Journal of Molecular Sciences, Vol 20, Iss 9, p

2019 Volume 2268

Abstract	Current organ shortages have led centers to extend the acceptance criteria for organs, increasing the risk for adverse outcomes. Current preservation protocols have not been adapted so as to efficiently protect these organs. Herein, we target oxidative stress, the key mechanism of ischemia reperfusion injury. Vectisol ® is a novel antioxidant strategy based on the encapsulation of resveratrol into a cyclodextrin, increasing its bioavailability. We tested this compound as an additive to the most popular static preservation solutions and machine perfusion (LifePort) in a preclinical pig model of kidney autotransplantation. In regard to static preservation, supplementation improved glomerular filtration and proximal tubular function early recovery. Extended follow-up confirmed the higher level of protection, slowing chronic loss of function (creatininemia and proteinuria) and the onset of histological lesions. Regarding machine perfusion, the use of Vectisol ® decreased oxidative stress and apoptosis at the onset of reperfusion (30 min post declamping). Improved quality was confirmed with decreased early levels of circulating SOD (Superoxide Dismutase) and ASAT (asparagine amino transferase). Supplementation slowed the onset of chronic loss of function, as well as interstitial fibrosis and tubular atrophy. The simple addition of Vectisol ® to the preservation solution significantly improved the performance of organ preservation, with long-term effects on the outcome. This strategy is thus a key player for future multi-drug therapy aimed at ischemia reperfusion in transplantation.
Keywords	ischemia reperfusion injury ; transplantation ; organ preservation ; oxidative stress ; resveratrol ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2019-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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