Dataset Information

Pin2025_Intestinal Organoids Model

ABSTRACT: We have developed a human small intestinal organoid (hSIO)-based mathematical modelling approach for the early prediction of GI toxicity of oral antiproliferative cancer treatments. Our mathematical model comprises hSIOs proliferative cells that become non-proliferative and eventually undergo cell death. Negative feedback loops regulate the rate of transition between these states, enhancing proliferation during the organoid expansion phase and balancing cell death in the stationary phase. Furthermore, the stationary phase is eventually followed by organoid decay, if organoids are not split and medium refreshment is not performed, which we modelled by accounting for the toxic effect of accumulated cell-produced waste material. Regarding drug-induced toxicity, the model implements cycle arrest and cell death of proliferative cells associated with exposure of oncology drugs

SUBMITTER: Carmen Pin

PROVIDER: MODEL2509110001 | BioModels | 2026-05-01

REPOSITORIES: BioModels

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Publications

Intestinal Organoid-Based Mathematical Modeling Predicts Clinical Gastrointestinal Toxicity of Oral Oncology Drugs.

Pin Carmen C Maheshvare M Deepa D Gall Louis L Hall Andrew A Coen Muireann M Bianco Ambra A Liu Shimeng S Pryde Kenneth K

CPT: pharmacometrics & systems pharmacology 20260501 5

Gastrointestinal (GI) toxicity is a common and potentially severe side effect of antiproliferative cancer therapies that often requires dose reduction or treatment interruption. Despite the clinical implications, there are currently no robust strategies for quantitative preclinical assessment of GI toxicity. We have developed a human small intestinal organoid (hSIO)-based mathematical modeling approach for the early prediction of GI toxicity of oral antiproliferative cancer treatments. Our appro ...[more]

PMID: 42033153

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Project description:Constituting the final growth phase during the lifecycle of maize (Zea Mays L.), leaf senescence plays an important biological role in grain yield in crops. We undertook proteomic and physiological analyses in inbred line Yu816 in order to unravel the underlying mechanisms of leaf senescence induced by preventing pollination. A total of 6,941 proteins were identified by Isobaric tags for Relative and Absolute Quantitation (iTRAQ) analysis. Proteomic analyses between pollinated (POL) and non-pollinated (NONPOL) plants indicated that 973 different proteins accumulated in NONPOL plants. The accumulated proteins were classified into various groups, including response to stimuli, cellular processes, cell death and metabolic processes using functional analysis. Furthermore, in accordance with the changes in these different accumulated proteins, analysis of changes in leaf total soluble sugars and starch content showed that the prevention of pollination can disturb endogenousplant hormone and sugar metabolism and lead to ROS bursts, protein degradation and photosystem breakdown, eventually resulting in leaf senescence. This represents the first attempt at global proteome profiling in response to induced leaf senescence by preventing pollination in maize, and provides a better understanding of the molecular mechanisms involved in induced leaf senescence.Constituting the final growth phase during the lifecycle of maize (Zea Mays L.), leaf senescence plays an important biological role in grain yield in crops. We undertook proteomic and physiological analyses in inbred line Yu816 in order to unravel the underlying mechanisms of leaf senescence induced by preventing pollination. A total of 6,941 proteins were identified by Isobaric tags for Relative and Absolute Quantitation (iTRAQ) analysis. Proteomic analyses between pollinated (POL) and non-pollinated (NONPOL) plants indicated that 973 different proteins accumulated in NONPOL plants. The accumulated proteins were classified into various groups, including response to stimuli, cellular processes, cell death and metabolic processes using functional analysis. Furthermore, in accordance with the changes in these different accumulated proteins, analysis of changes in leaf total soluble sugars and starch content showed that the prevention of pollination can disturb endogenousplant hormone and sugar metabolism and lead to ROS bursts, protein degradation and photosystem breakdown, eventually resulting in leaf senescence. This represents the first attempt at global proteome profiling in response to induced leaf senescence by preventing pollination in maize, and provides a better understanding of the molecular mechanisms involved in induced leaf senescence.

Project description:A long-term-survival (LTS) phase in Listeria monocytogenes was recently discovered. Cells in this phase are coccoid in shape, survive for at least 30 d without any decrease in viable cell numbers, and are very resistant to heat and high pressure. However, how cells of L. monocytogenes transition to this long-term-survival phase is little understood. Therefore, a whole-genome expression analysis was conducted to study the transcription profile of L. monocytogenes as it enters the LTS phase. Transcription profiles at log, stationary and death phases were analyzed since differential gene expressions at these phases may contribute to the eventual transition to the LTS phase. Specifically, cells of L. monocytogenes F2365 at log, stationary, death and LTS phases were obtained by incubating cultures in TSBYE at 35°C for 13 h, 17 h, 24 h and 168-336 h, respectively. Also, to study cells transitioning from the LTS phase back to the log phase, 1 ml of the LTS-phase culture at 336 h was reinoculated into 100 ml of fresh TSBYE with incubation at 35°C for 8 h. Total RNAs of all samples were extracted, reverse transcribed into cDNAs and then hybridized to the L. monocytogenes expression microarray (Roche NimbleGen). During the transition from log phase to stationary phase, differential changes in gene expression involved genes associated with cell envelope, cell division, stress response, energy metabolism, protein synthesis and material transport. During the transition from stationary to death phase, differential changes were observed in genes related to cell envelope, detoxification, pathogenesis, energy metabolism, protein synthesis and material transport. When cultures transitioned from death phase to 168-h LTS phase, significant downregulation of genes associated with amino acid and protein biosynthesis, as well as stress responses, were observed (P < 0.05), while multiple genes related to cell envelope, energy production and material transportation were significantly upregulated (P < 0.05). High similarity of transcription profiles (r = 0.93) within LTS phase was observed when comparing transcriptomes at 168 h and 336 h. RNA quality measurement revealed a high level of degradation of ribosomal RNA during the LTS phase. The transcription profile at 8-h (log-phase) after re-inoculation of LTS cells also resembled that at 13 h (r = 0.94). We hypothesize that the upregulation of some compatible solute transporters during the LTS phase may result in accumulation of these solutes, which may lower intracellular water activity and thus enhance resistance of L. monocytogenes to heat and high pressure. Dormancy may be induced at the LTS phase which is suggested by the downregulation of genes associated with transcription and translation. Once fresh nutrients are provided, LTS cells may quickly exit dormancy and become metabolically active as they transition to the log phase.

Dataset Information

Pin2025_Intestinal Organoids Model

Publications

Intestinal Organoid-Based Mathematical Modeling Predicts Clinical Gastrointestinal Toxicity of Oral Oncology Drugs.

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