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Article ; Online: The Extracorporeal Proteome-The Significance of Selective Protein Removal During Dialysis Therapy.

Kratochwill, Klaus

2018 Volume 12, Issue 6, Page(s) e1800078

Abstract: Dialysis as renal replacement therapy aims excess water and waste solutes from the uremic patient while retaining proteins in the plasma. Irrespective of the dialysis modality, hemodialysis (HD) or peritoneal dialysis (PD), the amount and composition of ... ...

Abstract	Dialysis as renal replacement therapy aims excess water and waste solutes from the uremic patient while retaining proteins in the plasma. Irrespective of the dialysis modality, hemodialysis (HD) or peritoneal dialysis (PD), the amount and composition of proteins that are removed are important determinants of the biocompatibility of the therapy. Although hemodialysis membranes would ideally be biologically inert filtration tubes, they are known to adsorb proteins. The part of the plasma proteome that is thereby removed during every dialysis session may be regarded as the extracorporeal proteome, which has to be kept in balance with the plasma proteome, regarding the individual proteins' biological roles and activation states. In a recent study, Ronci et al. (Proteomics Clin. Appl. 2018, e1700140) comprehensively compare two hemodialyzer membrane materials by shotgun LC-MS proteomic analysis of adsorbed proteins and ultrafiltrates from four HD patients. While pathway analysis is an attractive tool to compare different proteomes on an abstract level, some challenges remain regarding the adaptation for such tools for special proteomes and the interpretation of relative changes compared absolute changes regarding their biological importance in dialysis techniques. In summary, selective protein removal may represent a yet unexploited therapeutic opportunity if the "right" proteins are removed from the blood.
MeSH term(s)	Cellulose/analogs & derivatives ; Humans ; Peritoneal Dialysis ; Proteome ; Proteomics ; Renal Dialysis
Chemical Substances	Proteome ; Cellulose (9004-34-6) ; cellulose triacetate (9012-09-3)
Language	English
Publishing date	2018-09-24
Publishing country	Germany
Document type	Journal Article ; Comment
ZDB-ID	2261788-7
ISSN	1862-8354 ; 1862-8346
ISSN (online)	1862-8354
ISSN	1862-8346
DOI	10.1002/prca.201800078
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Article ; Online: Proteomic study of mesothelial and endothelial cross-talk: key lessons.

Sacnun, Juan Manuel / Herzog, Rebecca / Kratochwill, Klaus

Expert review of proteomics

2023 Volume 19, Issue 7-12, Page(s) 289–296

Abstract: Introduction: The peritoneum, pleura, and pericardium are yet understudied multicellular systems where mesothelial cells (MCs) and endothelial cells (ECs) are in close proximity. Crosstalk between these cell types likely plays role in molecular ... ...

Abstract	Introduction: The peritoneum, pleura, and pericardium are yet understudied multicellular systems where mesothelial cells (MCs) and endothelial cells (ECs) are in close proximity. Crosstalk between these cell types likely plays role in molecular transport, immunological reactions, and metabolic processes in health, disease, and therapeutic intervention. Areas covered: In this review, we discuss recent proteomic efforts to characterize the crosstalk between MC and EC. We describe the proteomic methods necessary for investigation of crosstalk between MC and EC, as well as the in-vitro models that can be employed. Potential experimental approaches range from conditioned medium, via co-culture on semi-permeable membranes, to 3D cell culture based organoid models. While the biological and clinical relevance of the models may increase with their ability to mimic close cell communication, the practicality of these complex experiments corresponds vice versa, making standardization more difficult and expensive. Expert opinion: Currently, data and reports on mesothelial-to-endothelial crosstalk are still very scarce. In our opinion, the in-vitro model using semi-permeable cell culture inserts will allow to establish a basic understanding of cellular crosstalk that may occur between those cell types. Later-on, more sophisticated 3D cell cultures may be better able to simulate the transport dynamics within the peritoneal membrane.
MeSH term(s)	Humans ; Endothelial Cells/metabolism ; Epithelial Cells/metabolism ; Proteomics/methods ; Peritoneum
Language	English
Publishing date	2023-02-06
Publishing country	England
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2299100-1
ISSN	1744-8387 ; 1478-9450
ISSN (online)	1744-8387
ISSN	1478-9450
DOI	10.1080/14789450.2023.2174851
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Article: Spatial Proteomics for the Molecular Characterization of Breast Cancer.

Brožová, Klára / Hantusch, Brigitte / Kenner, Lukas / Kratochwill, Klaus

Proteomes

2023 Volume 11, Issue 2

Abstract: Breast cancer (BC) is a major global health issue, affecting a significant proportion of the female population and contributing to high rates of mortality. One of the primary challenges in the treatment of BC is the disease's heterogeneity, which can ... ...

Abstract	Breast cancer (BC) is a major global health issue, affecting a significant proportion of the female population and contributing to high rates of mortality. One of the primary challenges in the treatment of BC is the disease's heterogeneity, which can lead to ineffective therapies and poor patient outcomes. Spatial proteomics, which involves the study of protein localization within cells, offers a promising approach for understanding the biological processes that contribute to cellular heterogeneity within BC tissue. To fully leverage the potential of spatial proteomics, it is critical to identify early diagnostic biomarkers and therapeutic targets, and to understand protein expression levels and modifications. The subcellular localization of proteins is a key factor in their physiological function, making the study of subcellular localization a major challenge in cell biology. Achieving high resolution at the cellular and subcellular level is essential for obtaining an accurate spatial distribution of proteins, which in turn can enable the application of proteomics in clinical research. In this review, we present a comparison of current methods of spatial proteomics in BC, including untargeted and targeted strategies. Untargeted strategies enable the detection and analysis of proteins and peptides without a predetermined molecular focus, whereas targeted strategies allow the investigation of a predefined set of proteins or peptides of interest, overcoming the limitations associated with the stochastic nature of untargeted proteomics. By directly comparing these methods, we aim to provide insights into their strengths and limitations and their potential applications in BC research.
Language	English
Publishing date	2023-05-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720995-7
ISSN	2227-7382
ISSN	2227-7382
DOI	10.3390/proteomes11020017
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Article ; Online: OntoloViz: a GUI for interactive visualization of ranked disease or drug lists using the MeSH and ATC ontologies.

Ley, Matthias / Heinzel, Andreas / Fillinger, Lucas / Kratochwill, Klaus / Perco, Paul

Bioinformatics advances

2023 Volume 3, Issue 1, Page(s) vbad113

Abstract: Motivation: Structured vocabularies for drugs and diseases represent, besides their primary use for annotating scientific literature or scientific information in general, a valuable resource for visualizing aggregated information. The Medical Subject ... ...

Abstract	Motivation: Structured vocabularies for drugs and diseases represent, besides their primary use for annotating scientific literature or scientific information in general, a valuable resource for visualizing aggregated information. The Medical Subject Headings (MeSH) and Anatomical Therapeutic Chemical (ATC) ontologies are widely used structured vocabularies for diseases and drugs, respectively. Their hierarchical tree-like structure can be used as a basis for creating intuitive visual displays for specific diseases and drugs within their higher-order classifications. Such displays are helpful means to contextualize diseases and drugs in various settings such as in drug repositioning. However, there are few tools that can harness the potential of these structured ontologies to create informative visual representations without extensive programming and data processing skills. Results: We have developed OntoloViz, a Graphical User Interface (GUI) for visualizing annotated lists of drugs or diseases in the context of their MeSH or ATC ontologies in an intuitively interpretable sunburst layout. Minimum input is a list of disease or drug names. Users in addition have the option to specify numerical parameters for the input lists to enhance the visualization, e.g. to visualize term frequencies. The GUI allows values to be propagated upwards in the respective ontology tree structure thus facilitating exploration of gene and drug lists. We present two use cases for OntoloViz, namely (i) a graphical representation of clinically tested drugs for coronavirus disease (COVID-19) based on ATC Classification and (ii) a graphical representation of literature annotation of human diseases on the MeSH ontology. Availability and implementation: The OntoloViz package can be retrieved from PyPi. The source code along with test data, template, and documentations are available at GitHub (https://github.com/Delta4AI/OntoloViz).
Language	English
Publishing date	2023-08-23
Publishing country	England
Document type	Journal Article
ISSN	2635-0041
ISSN (online)	2635-0041
DOI	10.1093/bioadv/vbad113
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Article ; Online: Bone Allograft Acid Lysates Change the Genetic Signature of Gingival Fibroblasts.

Panahipour, Layla / Abbasabadi, Azarakhsh Oladzad / Wagner, Anja / Kratochwill, Klaus / Pichler, Monika / Gruber, Reinhard

International journal of molecular sciences

2023 Volume 24, Issue 22

Abstract: Bone allografts are widely used as osteoconductive support to guide bone regrowth. Bone allografts are more than a scaffold for the immigrating cells as they maintain some bioactivity of the original bone matrix. Yet, it remains unclear how immigrating ... ...

Abstract	Bone allografts are widely used as osteoconductive support to guide bone regrowth. Bone allografts are more than a scaffold for the immigrating cells as they maintain some bioactivity of the original bone matrix. Yet, it remains unclear how immigrating cells respond to bone allografts. To this end, we have evaluated the response of mesenchymal cells exposed to acid lysates of bone allografts (ALBA). RNAseq revealed that ALBA has a strong impact on the genetic signature of gingival fibroblasts, indicated by the increased expression of IL11, AREG, C11orf96, STC1, and GK-as confirmed by RT-PCR, and for IL11 and STC1 by immunoassays. Considering that transforming growth factor-β (TGF-β) is stored in the bone matrix and may have caused the expression changes, we performed a proteomics analysis, TGF-β immunoassay, and smad2/3 nuclear translocation. ALBA neither showed detectable TGF-β nor was the lysate able to induce smad2/3 translocation. Nevertheless, the TGF-β receptor type I kinase inhibitor SB431542 significantly decreased the expression of IL11, AREG, and C11orf96, suggesting that other agonists than TGF-β are responsible for the robust cell response. The findings suggest that IL11, AREG, and C11orf96 expression in mesenchymal cells can serve as a bioassay reflecting the bioactivity of the bone allografts.
MeSH term(s)	Interleukin-11/metabolism ; Transforming Growth Factor beta/metabolism ; Gingiva/metabolism ; Fibroblasts/metabolism ; Allografts/metabolism ; Cells, Cultured
Chemical Substances	Interleukin-11 ; Transforming Growth Factor beta
Language	English
Publishing date	2023-11-10
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/ijms242216181
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Article ; Online: A Meta-Analysis of Human Transcriptomics Data in the Context of Peritoneal Dialysis Identifies Novel Receptor-Ligand Interactions as Potential Therapeutic Targets.

Evgeniou, Michail / Sacnun, Juan Manuel / Kratochwill, Klaus / Perco, Paul

International journal of molecular sciences

2021 Volume 22, Issue 24

Abstract: Peritoneal dialysis (PD) is one therapeutic option for patients with end-stage kidney disease (ESKD). Molecular profiling of samples from PD patients using different Omics technologies has led to the discovery of dysregulated molecular processes due to ... ...

Abstract	Peritoneal dialysis (PD) is one therapeutic option for patients with end-stage kidney disease (ESKD). Molecular profiling of samples from PD patients using different Omics technologies has led to the discovery of dysregulated molecular processes due to PD treatment in recent years. In particular, a number of transcriptomics (TX) datasets are currently available in the public domain in the context of PD. We set out to perform a meta-analysis of TX datasets to identify dysregulated receptor-ligand interactions in the context of PD-associated complications. We consolidated transcriptomics profiles from twelve untargeted genome-wide gene expression studies focusing on human cell cultures or samples from human PD patients. Gene set enrichment analysis was used to identify enriched biological processes. Receptor-ligand interactions were identified using data from CellPhoneDB. We identified 2591 unique differentially expressed genes in the twelve PD studies. Key enriched biological processes included angiogenesis, cell adhesion, extracellular matrix organization, and inflammatory response. We identified 70 receptor-ligand interaction pairs, with both interaction partners being dysregulated on the transcriptional level in one of the investigated tissues in the context of PD. Novel receptor-ligand interactions without prior annotation in the context of PD included BMPR2-GDF6, FZD4-WNT7B, ACKR2-CCL2, or the binding of EPGN and EREG to the EGFR, as well as the binding of SEMA6D to the receptors KDR and TYROBP. In summary, we have consolidated human transcriptomics datasets from twelve studies in the context of PD and identified sets of novel receptor-ligand pairs being dysregulated in the context of PD that warrant investigation in future functional studies.
MeSH term(s)	Computational Biology ; Gene Expression Profiling ; Humans ; Kidney Failure, Chronic/genetics ; Kidney Failure, Chronic/therapy ; Peritoneal Dialysis ; Transcriptome
Language	English
Publishing date	2021-12-10
Publishing country	Switzerland
Document type	Journal Article ; Meta-Analysis
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222413277
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Article ; Online: Publisher Correction: Assessing mechanical catheter dysfunction in automated tidal peritoneal dialysis using cycler software: a case control, proof-of-concept study.

Flores, Krystell Oviedo / Kaltenegger, Lukas / Eibensteiner, Fabian / Unterwurzacher, Markus / Kratochwill, Klaus / Aufricht, Christoph / König, Franz / Vychytil, Andreas

Scientific reports

2022 Volume 12, Issue 1, Page(s) 7623

Language	English
Publishing date	2022-05-10
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-12074-y
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Article: In-Depth Analysis of the Extracorporeal Proteome Adsorbed to Dialysis Membranes during Hemodialysis.

Daniel-Fischer, Lisa / Sobieszek, Isabel J / Wagner, Anja / Sacnun, Juan Manuel / Watschinger, Bruno / Aufricht, Christoph / Kratochwill, Klaus / Herzog, Rebecca

Membranes

2022 Volume 12, Issue 11

Abstract: Used hemodialysis membranes (HD-M) are a valuable reservoir of biological information. Proteins bind to HD-M, but whether this process depends on the type of membrane or patient factors or selectively affects specific protein classes has not been ... ...

Abstract	Used hemodialysis membranes (HD-M) are a valuable reservoir of biological information. Proteins bind to HD-M, but whether this process depends on the type of membrane or patient factors or selectively affects specific protein classes has not been adequately elucidated. State-of-the-art proteomics techniques are capable of identifying and quantifying this therapy-specific subproteome to enable the analysis of disease- or membrane-induced pathophysiologies. We demonstrate the feasibility of the deep proteomic characterization of the extracorporeal proteome adsorbed to HD-M. A shotgun proteomics approach using nano-flow liquid chromatography coupled to mass-spectrometry identified 1648 unique proteins eluted by a chaotropic buffer from the HD-M of eight patients. In total, 995 proteins were present in all eluates; a more stringent approach showed that a core proteome of 310 proteins could be identified independently in all samples. Stability of the dialyzer proteome was demonstrated by a >90% re-identification rate on longitudinal samples of a single patient. The core proteome showed an overrepresentation of pathways of hemostasis and the immune system, and showed differences in membrane materials (polysulfone vs. helixone). This study demonstrates that optimized conditions combined with high-performance proteomics enable the in-depth exploration of the subproteome bound to HD-M, yielding a stable core proteome that can be exploited to study patient-specific factors and improve hemodialysis therapy.
Language	English
Publishing date	2022-11-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2614641-1
ISSN	2077-0375
ISSN	2077-0375
DOI	10.3390/membranes12111120
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Article ; Online: Proteome-Wide Differential Effects of Peritoneal Dialysis Fluid Properties in an In Vitro Human Endothelial Cell Model.

Sacnun, Juan Manuel / Hoogenboom, Robin / Eibensteiner, Fabian / Sobieszek, Isabel J / Unterwurzacher, Markus / Wagner, Anja / Herzog, Rebecca / Kratochwill, Klaus

International journal of molecular sciences

2022 Volume 23, Issue 14

Abstract: To replace kidney function, peritoneal dialysis (PD) utilizes hyperosmotic PD fluids with specific physico-chemical properties. Their composition induces progressive damage of the peritoneum, leading to vasculopathies, decline of membrane function, and ... ...

Abstract	To replace kidney function, peritoneal dialysis (PD) utilizes hyperosmotic PD fluids with specific physico-chemical properties. Their composition induces progressive damage of the peritoneum, leading to vasculopathies, decline of membrane function, and PD technique failure. Clinically used PD fluids differ in their composition but still remain bioincompatible. We mapped the molecular pathomechanisms in human endothelial cells induced by the different characteristics of widely used PD fluids by proteomics. Of 7894 identified proteins, 3871 were regulated at least by 1 and 49 by all tested PD fluids. The latter subset was enriched for cell junction-associated proteins. The different PD fluids individually perturbed proteins commonly related to cell stress, survival, and immune function pathways. Modeling two major bioincompatibility factors of PD fluids, acidosis, and glucose degradation products (GDPs) revealed distinct effects on endothelial cell function and regulation of cellular stress responses. Proteins and pathways most strongly affected were members of the oxidative stress response. Addition of the antioxidant and cytoprotective additive, alanyl-glutamine (AlaGln), to PD fluids led to upregulation of thioredoxin reductase-1, an antioxidant protein, potentially explaining the cytoprotective effect of AlaGln. In conclusion, we mapped out the molecular response of endothelial cells to PD fluids, and provided new evidence for their specific pathomechanisms, crucial for improvement of PD therapies.
MeSH term(s)	Antioxidants/pharmacology ; Dialysis Solutions/chemistry ; Endothelial Cells/metabolism ; Glucose/metabolism ; Humans ; Peritoneal Dialysis/adverse effects ; Peritoneum/metabolism ; Proteome/metabolism
Chemical Substances	Antioxidants ; Dialysis Solutions ; Proteome ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-07-20
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/ijms23148010
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Article ; Online: Assessing mechanical catheter dysfunction in automated tidal peritoneal dialysis using cycler software: a case control, proof-of-concept study.

Oviedo Flores, Krystell / Kaltenegger, Lukas / Eibensteiner, Fabian / Unterwurzacher, Markus / Kratochwill, Klaus / Aufricht, Christoph / König, Franz / Vychytil, Andreas

Scientific reports

2022 Volume 12, Issue 1, Page(s) 5657

Abstract: New recommendations on evaluation of peritoneal membrane function suggest ruling out catheter dysfunction when evaluating patients with low ultrafiltration capacity. We introduce the use of a combination of parameters obtained from the cycler software PD ...

Abstract	New recommendations on evaluation of peritoneal membrane function suggest ruling out catheter dysfunction when evaluating patients with low ultrafiltration capacity. We introduce the use of a combination of parameters obtained from the cycler software PD Link with HomeChoicePro (Baxter International Inc., Illinois, United States) cyclers for predicting catheter dysfunction in automated peritoneal dialysis patients (APD). Out of 117 patients treated at the Medical University of Vienna between 2015 and 2021, we retrospectively identified all patients with verified catheter dysfunction (n = 14) and compared them to controls without clinical evidence of mechanical catheter problems and a recent X-ray confirming PD catheter tip in the rectovesical/rectouterine space (n = 19). All patients had a coiled single-cuff PD catheter, performed tidal PD, and received neutral pH bicarbonate/lactate-buffered PD fluids with low-glucose degradation products on APD. Icodextrin-containing PD fluids were used for daytime dwells. We retrieved cycler data for seven days each and tested parameters' predictive capability of catheter dysfunction. Total number of alarms/week > 7 as single predictive parameter of catheter dislocation identified 85.7% (sensitivity) of patients with dislocated catheter, whereas 31.6% (1-specificity) of control patients were false positive. A combination of parameters (number of alarms/week > 7, total drain time > 22 min, ultrafiltration of last fill < 150 mL) where at least two of three parameters appeared identified the same proportion of patients with catheter dislocation, but was more accurate in identifying controls (21.1% false positive). In contrast to yearly PET measurements, an easily applicable combination of daily cycler readout parameters, also available in new APD systems connected to remote monitoring platforms shows potential for diagnosis of catheter dysfunction during routine follow-up.
MeSH term(s)	Catheters ; Dialysis Solutions/adverse effects ; Glucose/metabolism ; Humans ; Peritoneal Dialysis/adverse effects ; Retrospective Studies ; Software
Chemical Substances	Dialysis Solutions ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-04-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-09462-9
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