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377 Publications visible to you, out of a total of 377
On the mechanisms of biliary flux

Abstract

Not specified

Authors: Nachiket Vartak, Dirk Drasdo, Fabian Geisler, Tohru Itoh, Ronald P.J. Oude Elferink, Stan F.J. van de Graaf, John Chiang, Verena Keitel, Michael Trauner, Peter Jansen, Jan G Hengstler

Date Published: 23rd Jun 2021

Publication Type: Journal

Open modeling and exchange (OMEX) metadata specification version 1.0

Abstract (Expand)

A standardized approach to annotating computational biomedical models and their associated files can facilitate model reuse and reproducibility among research groups, enhance search and retrieval of … models and data, and enable semantic comparisons between models. Motivated by these potential benefits and guided by consensus across the COmputational Modeling in BIology NEtwork (COMBINE) community, we have developed a specification for encoding annotations in Open Modeling and EXchange (OMEX)-formatted archives. Distributing modeling projects within these archives is a best practice established by COMBINE, and the OMEX metadata specification presented here provides a harmonized, community-driven approach for annotating a variety of standardized model and data representation formats within an archive. The specification primarily includes technical guidelines for encoding archive metadata, so that software tools can more easily utilize and exchange it, thereby spurring broad advancements in model reuse, discovery, and semantic analyses.

Authors: Maxwell L. Neal, John H. Gennari, Dagmar Waltemath, David P. Nickerson, Matthias König

Date Published: 25th Jun 2020

Publication Type: Journal

Optimality in COVID-19 vaccination strategies determined by heterogeneity in human-human interaction networks

Abstract (Expand)

Interactions between humans cause transmission of SARS-CoV-2. We demonstrate that heterogeneity in human-human interactions give rise to non-linear infection networks that gain complexity with time. … Consequently, targeted vaccination strategies are challenged as such effects are not accurately captured by epidemiological models assuming homogeneous mixing. With vaccines being prepared for global deployment determining optimality for swiftly reaching population level immunity in heterogeneous local communities world-wide is critical. We introduce a model that predicts the effect of vaccination into an ongoing COVID-19 outbreak using precision simulation of human-human interaction and infection networks. We show that simulations incorporating non-linear network complexity and local heterogeneity can enable governance with performance-quantified vaccination strategies. Vaccinating highly interactive people diminishes the risk for an infection wave, while vaccinating the elderly reduces fatalities at low population level immunity. Interestingly, a combined strategy is not better due to non-linear effects. While risk groups should be vaccinated first to minimize fatalities, significant optimality branching is observed with increasing population level immunity. Importantly, we demonstrate that regardless of immunization strategy non-pharmaceutical interventions are required to prevent ICU overload and breakdown of healthcare systems. The approach, adaptable in real-time and applicable to other viruses, provides a highly valuable platform for the current and future pandemics.

Authors: Bjoern Goldenbogen, Stephan O. Adler, Oliver Bodeit, Judith AH Wodke, Ximena Escalera-Fanjul, Aviv Korman, Maria Krantz, Lasse Bonn, Rafael U Morán-Torres, Johanna E L Haffner, Maxim Karnetzki, Ivo Maintz, Lisa Mallis, Patrick S Segelitz, Martin Seeger, Rune Linding, Edda Klipp

Date Published: No date defined

Publication Type: Unpublished

Optimization of extracellular matrix for primary human hepatocyte cultures using mixed collagen-Matrigel matrices.

Abstract (Expand)

Loss of differentiation of primary human hepatocytes (PHHs) ex vivo is a known problem of in vitro liver models. Culture optimizations using collagen type I and Matrigel reduce the dedifferentiation … process but are not able to prevent it. While neither of these extracellular matrices (ECMs) on their own correspond to the authentic hepatic ECM, a combination of them could more closely resemble the in vivo situation. Our study aimed to systematically analyze the influence of mixed matrices composed of collagen type I and Matrigel on the maintenance and reestablishment of hepatic functions. Therefore, PHHs were cultured on mixed collagen-Matrigel matrices in monolayer and sandwich cultures and viability, metabolic capacity, differentiation markers, cellular arrangement and the cells' ability to repolarize and form functional bile canaliculi were assessed by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), functional assays and immunofluorescence microscopy. Our results show that mixed matrices were superior to pure matrices in maintaining metabolic capacity and hepatic differentiation. In contrast, Matrigel supplementation can impair the development of a proper hepatocytic polarization. Our systematic study helps to compose an optimized ECM to maintain and reestablish hepatic differentiation on cellular and multicellular levels in human liver models.

Authors: L. Seidemann, S. Prinz, J. C. Scherbel, C. Gotz, D. Seehofer, G. Damm

Date Published: 20th Jan 2023

Publication Type: Journal

Orphan nuclear receptor ERR-γ regulates hepatic FGF23 production in acute kidney injury.

Abstract (Expand)

Fibroblast growth factor 23 (FGF23), a hormone generally derived from bone, is important in phosphate and vitamin D homeostasis. In acute kidney injury (AKI) patients, high-circulating FGF23 levels are … associated with disease progression and mortality. However, the organ and cell type of FGF23 production in AKI and the molecular mechanism of its excessive production are still unidentified. For insight, we investigated folic acid (FA)-induced AKI in mice. Interestingly, simultaneous with FGF23, orphan nuclear receptor ERR-γ expression is increased in the liver of FA-treated mice, and ectopic overexpression of ERR-γ was sufficient to induce hepatic FGF23 production. In patients and in mice, AKI is accompanied by up-regulated systemic IL-6, which was previously identified as an upstream regulator of ERR-γ expression in the liver. Administration of IL-6 neutralizing antibody to FA-treated mice or of recombinant IL-6 to healthy mice confirms IL-6 as an upstream regulator of hepatic ERR-γ-mediated FGF23 production. A significant (<i>P</i> &lt; 0.001) interconnection between high IL-6 and FGF23 levels as a predictor of AKI in patients that underwent cardiac surgery was also found, suggesting the clinical relevance of the finding. Finally, liver-specific depletion of ERR-γ or treatment with an inverse ERR-γ agonist decreased hepatic FGF23 expression and plasma FGF23 levels in mice with FA-induced AKI. Thus, inverse agonist of ERR-γ may represent a therapeutic strategy to reduce adverse plasma FGF23 levels in AKI.

Authors: Kamalakannan Radhakrishnan, Yong-Hoon Kim, Yoon Seok Jung, Don-Kyu Kim, Soon-Young Na, Daejin Lim, Dong Hun Kim, Jina Kim, Hyung-Seok Kim, Hyon E Choy, Sung Jin Cho, In-Kyu Lee, Şamil Ayvaz, Stefanie Nittka, Danilo Fliser, Stefan J Schunk, Thimoteus Speer, Steven Dooley, Chul-Ho Lee, Hueng-Sik Choi

Date Published: 20th Apr 2021

Publication Type: Journal

Orphan nuclear receptor ERRγ is a key regulator of human fibrinogen gene expression

Abstract

Not specified

Authors: Yaochen Zhang, Don-Kyu Kim, Yan Lu, Yoon Seok Jung, Ji-min Lee, Young-Hoon Kim, Yong Soo Lee, Jina Kim, Bedair Dewidar, Won-IL Jeong, In-Kyu Lee, Sung Jin Cho, Steven Dooley, Chul-Ho Lee, Xiaoying Li, Hueng-Sik Choi

Date Published: 27th Jul 2017

Publication Type: Not specified

Orphan Nuclear Receptor ERRγ Is a Novel Transcriptional Regulator of IL-6 Mediated Hepatic BMP6 Gene Expression in Mice

Abstract

Not specified

Authors: Kamalakannan Radhakrishnan, Yong-Hoon Kim, Yoon Seok Jung, Jina Kim, Don-Kyu Kim, Sung Jin Cho, In-Kyu Lee, Steven Dooley, Chul-Ho Lee, Hueng-Sik Choi

Date Published: 1st Oct 2020

Publication Type: Journal

Orphan nuclear receptor SHP regulates iron metabolism through inhibition of BMP6-mediated hepcidin expression.

Abstract (Expand)

Small heterodimer partner (SHP) is a transcriptional corepressor regulating diverse metabolic processes. Here, we show that SHP acts as an intrinsic negative regulator of iron homeostasis. SHP-deficient … mice maintained on a high-iron diet showed increased serum hepcidin levels, decreased expression of the iron exporter ferroportin as well as iron accumulation compared to WT mice. Conversely, overexpression of either SHP or AMP-activated protein kinase (AMPK), a metabolic sensor inducing SHP expression, suppressed BMP6-induced hepcidin expression. In addition, an inhibitory effect of AMPK activators metformin and AICAR on BMP6-mediated hepcidin gene expression was significantly attenuated by ablation of SHP expression. Interestingly, SHP physically interacted with SMAD1 and suppressed BMP6-mediated recruitment of the SMAD complex to the hepcidin gene promoter by inhibiting the formation of SMAD1 and SMAD4 complex. Finally, overexpression of SHP and metformin treatment of BMP6 stimulated mice substantially restored hepcidin expression and serum iron to baseline levels. These results reveal a previously unrecognized role for SHP in the transcriptional control of iron homeostasis.

Authors: D. K. Kim, Y. H. Kim, Y. S. Jung, K. S. Kim, J. H. Jeong, Y. S. Lee, J. M. Yuk, B. C. Oh, H. E. Choy, S. Dooley, M. U. Muckenthaler, C. H. Lee, H. S. Choi

Date Published: 1st Oct 2016

Publication Type: Not specified

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