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Zeilfelder2025 - Model for primary human hepatocytes (PHH)

ABSTRACT: Mathematical multi-compartment model described by sets of coupled ordinary differential equations (ODEs) for studying the IL6 and SMAD signaling in PHH cells.

SUBMITTER: Nantia Leonidou

PROVIDER: MODEL2503270002 | BioModels | 2025-11-13

REPOSITORIES: BioModels

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Diclofenac and acetaminophen dim the acute-phase response but amplify expression of the iron regulator hepcidin in liver cancer cells.

Zeilfelder Anja A Vanlier Joep J Mölders Christina C Kastl Philipp P Helm Barbara B Burbano de Lara Sebastian S Möcklinghoff Till T Leonidou Nantia N Holstein Elisa E Vlasov Artyom A Held Alexander A Wilken Silvana S Hoffmann Katrin K Schicht Gerda G Scheffschick Andrea A Katerinopoulou Markella M Giehl-Brown Esther E Kahlert Christoph C Michalski Christoph C Seehofer Daniel D Damm Georg G Muckenthaler Martina U MU Schilling Marcel M Timmer Jens J Klingmüller Ursula U

Cell systems 20251110 11

Cancer patients frequently suffer from anemia and cancer-related pain, which can be treated by non-opioid analgesics such as diclofenac (DCF) and acetaminophen (APAP) attenuating inflammatory responses. The pro-inflammatory cytokine interleukin (IL)-6 triggers the expression of acute-phase proteins, including the iron regulator hepcidin. Using proteomics and dynamic pathway modeling, we show that DCF and APAP directly impact IL-6 signaling by enhancing the induction of the feedback-inhibitor sup ...[more]

PMID: 41218607

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Zeilfelder2025 - Model for human liver cancer cell line HepG2

Project description:Mathematical multi-compartment model described by sets of coupled ordinary differential equations (ODEs) for studying the IL6 and SMAD signaling in HepG2 human cancer cell lines.

2025-11-13 | MODEL2503270001 | BioModels

Single-Injection Multi-Omics Analysis by Direct Infusion Mass Spectrometry

Project description:Combined multi-omics analysis of proteomics, metabolomics, and lipidomics requires separate liquid chromatography mass spectrometry (LC-MS), which limit throughput and increase costs, hindering the application of mass spectrometry-based multi-omics to large-scale analyses. Here, we present simultaneous multi-omics analysis by direct infusion (SMAD), an integrated platform leveraging ion mobility mass spectrometry and self-developed software tools to enable single injection multi-omics analysis without liquid chromatography. SMAD allows quantification of over 9,000 metabolite m/z features and over 1,300 proteins from the same sample in less than five minutes. We validated the efficiency and reliability of SMAD with three case studies. (1) mouse macrophages after M1/M2 polarization and senescence, (2) a pilot drug screen in human cells, and (3) large-scale high-throughput drug screening of mammalian cells in 96-well plates. Finally, relationships between proteomic and metabolomic data are discovered by machine learning and validated.

2025-07-02 | MSV000098413 | MassIVE

Identifying direct interactome and substrates of human thioredoxins in specific cellular components with new cysteine-reactive enrichable chemical cross-linkers

Project description:Identifying direct substrates of enzymes in specific cell compartment is challenging in methodology, but crucial for revealing unique cellular processes in different subcellular locations. Here we developed a comprehensive live cell cross-linking coupled mass spectrometry strategy to identify direct interactome of redox enzymes in subcellular level. We chemically synthesized two new enrichable bis-vinyl sulfone chemical cross-linker ePDES1 and ePDES2 with alkyne group, and firstly established two-step IMAC enrichment method for high efficiency cross-linking peptide enrichment. Based on high quality ePDES1 and ePDES2 cross-linking spectra, our method achieved identifying hundreds of direct interacting proteins and substrates cross-linking to active cysteine sites of TXN1 both in cytoplasm and nuclei and TXN2 in mitochondria. It is interesting to simultaneously identify proteins cross-linked to TXN1 active Cys32 and Cys73 responsible for denitrosylation and transnitrosylation, respectively. Our method firstly identified direct interactome and substrates of oxidoreductases in subcellular level, providing resources for precisely studying redox homeostasis in specific cell compartment.

2024-09-02 | PXD055461 |

Gene expression data from 131 human subjects in Detroit, Michigan

Project description:Background Complex diseases are often difficult to diagnose, treat and study due to the multi-factorial nature of the underlying etiology. Large data sets are now widely available that can be used to define novel, mechanistically distinct disease subtypes (endotypes) in a completely data-driven manner. However, significant challenges exist with regard to how to segregate individuals into suitable subtypes of the disease and understand the distinct biological mechanisms of each when the goal is to maximize the discovery potential of these data sets. Results A multi-step decision tree-based method is described for defining endotypes based on gene expression, clinical covariates, and disease indicators using childhood asthma as a case study. We attempted to use alternative approaches such as the Student’s t-test, single data domain clustering and the Modk-prototypes algorithm, which incorporates multiple data domains into a single analysis and none performed as well as the novel multi-step decision tree method. This new method gave the best segregation of asthmatics and non-asthmatics, and it provides easy access to all genes and clinical covariates that distinguish the groups. Conclusions The multi-step decision tree method described here will lead to better understanding of complex disease in general by allowing purely data-driven disease endotypes to facilitate the discovery of new mechanisms underlying these diseases. This application should be considered a complement to ongoing efforts to better define and diagnose known endotypes. When coupled with existing methods developed to determine the genetics of gene expression, these methods provide a mechanism for linking genetics and exposomics data and thereby accounting for both major determinants of disease. We collected peripheral blood samples from 131 children for RNA extraction and hybridization of target cDNA onto Affymetrix Human U133 Plus 2.0 whole genome array.

2013-11-12 | E-GEOD-35571 | biostudies-arrayexpress

Switch Enhancer Elements Control Cell Fate in Human Embryonic Stem Cells (BeadChip)

Project description:A small toolkit of morphogens is used repeatedly to direct development, raising the question of how context dictates interpretation of the same cue. One example is the TGFβ pathway that in human embryonic stem cells fulfills two opposite functions: pluripotency maintenance and mesendoderm (ME) specification. Using proteomics coupled to analysis of genome occupancy, we uncover a regulatory complex comprised of transcriptional effectors of the Hippo pathway (TAZ/YAP/TEAD), the TGFβ pathway (SMAD2/3) and the pluripotency regulator OCT4 (TSO). TSO collaborates with NuRD repressor complexes to buffer pluripotency gene expression, while suppressing ME genes. Importantly, the SMAD DNA binding partner FOXH1, a major specifier of ME, is found near TSO elements and upon fate specification we show that TSO is disrupted with subsequent SMAD-FOXH1 induction of ME. These studies define switch enhancer elements and provide a framework to understand how cellular context dictates interpretation of the same morphogen signal in development. Total RNA was isolated from human embryonic stem cells (WA09) 48h after siRNA transfection (siCntr, siTAZ/YAP, siTEAD1-4)

2013-12-18 | E-GEOD-52439 | biostudies-arrayexpress

Switch Enhancer Elements Control Cell Fate in Human Embryonic Stem Cells (ChIP-Seq)

Project description:A small toolkit of morphogens is used repeatedly to direct development, raising the question of how context dictates interpretation of the same cue. One example is the TGFβ pathway that in human embryonic stem cells fulfills two opposite functions: pluripotency maintenance and mesendoderm (ME) specification. Using proteomics coupled to analysis of genome occupancy, we uncover a regulatory complex comprised of transcriptional effectors of the Hippo pathway (TAZ/YAP/TEAD), the TGFβ pathway (SMAD2/3) and the pluripotency regulator OCT4 (TSO). TSO collaborates with NuRD repressor complexes to buffer pluripotency gene expression, while suppressing ME genes. Importantly, the SMAD DNA binding partner FOXH1, a major specifier of ME, is found near TSO elements and upon fate specification we show that TSO is disrupted with subsequent SMAD-FOXH1 induction of ME. These studies define switch enhancer elements and provide a framework to understand how cellular context dictates interpretation of the same morphogen signal in development. ChIP experiment, a total of 8 samples: 4 samples DMSO treated (Input ctr, IgG ctr, SMAD2 precipitation, TEAD4 precipitation), 4 samples SB431542 (Input ctr, IgG ctr, SMAD2 precipitation, TEAD4 precipitation)

2013-12-18 | E-GEOD-52437 | biostudies-arrayexpress

Transcription profiling of human CD14+ CD16- and CD14low CD16+ monocytes from patients with Sjogrens syndrome and normal controls

Project description:Sjogren's syndrome is an autoimmune disease, characterized by complaints such as xerostomia and keratoconjunctivitis sicca. In other autoimmune diseases such as diabetes and SLE, monocyte abberancies have been described. Therefore, this study aimed at studying the monocyte compartment in Sjogren's Syndrome, by transcription profiling of CD14+CD16- and CD14lowCD16+ monocytes in patients and controls.

2008-08-04 | E-MEXP-1242 | biostudies-arrayexpress

Gene expression data from 131 human subjects in Detroit, Michigan

2013-11-12 | GSE35571 | GEO

Human monocyte stimulation with IL6

Project description:Human monocyte stimulation with IL6

| PRJNA979179 | ENA

Genome-wide analysis of GATA1, GATA2, RUNX1, FLI1 and SCL binding in primary human megakaryocytes

Project description:We have mapped the binding sites for the five key regulators GATA1, GATA2, RUNX1, FLI1 and TAL1/SCL in primary human megakaryocytes. Statistical analysis identified subsets of enriched as well as depleted combinatorial binding patterns. In particular simultaneous binding by all 5 factors was highly enriched and occurred in the vicinity of many genes known to be involved in blood and megakaryocyte development. Knock down in zebrafish of 8 of these genes with no previously known role in hematopoiesis, revealed all to be essential for thrombocyte and/or erythroid development. Combinatorial analysis of multi-factor ChIP-Seq datasets coupled with a high-throughput in vivo screen therefore offers a powerful strategy to identify novel essential regulators of complex mammalian differentiation processes. 5 transcription factors and rabbit-IgG in megakaryocytes.

2011-06-01 | E-GEOD-24674 | biostudies-arrayexpress

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