PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Disease modeling”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2026

Zebrafish as a versatile model in biomedical research, from disease modeling to regenerative medicine: a review.

Zebrafish are an effective animal model widely utilized in biomedical research. They are known for their rapid reproduction and substantial genetic similarity to humans. Their transparent embryos directly enable the visualization of developmental processes and disease progression. This makes zebrafish invaluable for studying a broad range of human diseases, including cancer, cardiovascular disorders, and neurodegenerative conditions. Compared with other vertebrate models, zebrafish offer several advantages, including ease of genome editing, cost-effective maintenance, and suitability for high-throughput drug screening. Recent advancements have expanded the use of zebrafish in disease modeling and regenerative medicine, providing deeper insights into the genetic and cellular mechanisms underlying human pathologies. Zebrafish provide a robust platform for evaluating the safety, efficacy, and regenerative potential of both natural and synthetic biomaterials, including hydroxyapatite, bioactive glass nanoparticles, and bioceramics. This capability facilitates the creation of artificial tissues that closely resemble native structures. Additionally, integrating artificial intelligence technologies has improved automated data analysis and phenotyping in zebrafish studies, enhancing both accuracy and throughput. This review highlights current applications of zebrafish in disease modeling, drug discovery, regenerative medicine, and biomaterial assessment, emphasizing their evolving role as a versatile preclinical platform supported by advanced genetic and computational tools.

Animals↗
PubMed2026

A Landscape of Drosophila melanogaster Disease Models: From Genetic Platforms to Cross-Disease Mechanisms and Translational Research.

Modeling human diseases using the fruit fly (Drosophila melanogaster) has established itself as a cornerstone of functional genomics and preclinical medicine. Despite its anatomical simplicity, the Drosophila genome shares remarkable functional conservation with human disease-related genes, enabling the study of complex physiological traits through accessible tissue models. Furthermore, beyond individual disease models, we propose a framework demonstrating how these diseases converge at common molecular centers, such as the breakdown of protein homeostasis, mitochondrial dysfunction, chronic inflammation, and organ-to-organ communication. Finally, we discuss strategies for integrating the Drosophila platform into drug development pipelines and establishing standards to enhance inter-laboratory reproducibility. Overall, this review highlights the enduring value of fruit flies as a model system, particularly when combined with AI-omics approaches to transform complex biological datasets into actionable therapeutic strategies.

Drosophila↗
PubMed1978

Myocardial susceptibility to ischemic damage: a comparative study of disease models in the rat.

Using experimental models of various disease states, the ability of the isolated perfused working rat heart to withstand and recover from a period of severe ischemia was investigated. The results revealed that the coexistence of a diabetic state, obesity, or left ventricular hypertrophy increased the susceptibility of the hearts to ischemic damage and reduced the rate or the extent of postischemic recovery. In contrast, hearts obtained from moderately hypertensive rats exhibited a greater resistance to, and a superior recovery from, ischemia than did hearts obtained from normotensive controls.

Adenosine Triphosphate↗
PubMed2025

Correction of pathogenic mitochondrial DNA in patient-derived disease models using mitochondrial base editors.

Mutations in the mitochondrial genome can cause maternally inherited diseases, cancer, and aging-related conditions. Recent technological progress now enables the creation and correction of mutations in the mitochondrial genome, but it remains relatively unknown how patients with primary mitochondrial disease can benefit from this technology. Here, we demonstrate the potential of the double-stranded DNA deaminase toxin A-derived cytosine base editor (DdCBE) to develop disease models and therapeutic strategies for mitochondrial disease in primary human cells. Introduction of the m.15150G > A mutation in liver organoids resulted in organoid lines with varying degrees of heteroplasmy and correspondingly reduced ATP production, providing a unique model to study functional consequences of different levels of heteroplasmy of this mutation. Correction of the m.4291T > C mutation in patient-derived fibroblasts restored mitochondrial membrane potential. DdCBE generated sustainable edits with high specificity and product purity. To prepare for clinical application, we found that mRNA-mediated mitochondrial base editing resulted in increased efficiency and cellular viability compared to DNA-mediated editing. Moreover, we showed efficient delivery of the mRNA mitochondrial base editors using lipid nanoparticles, which is currently the most advanced non-viral in vivo delivery system for gene products. Our study thus demonstrates the potential of mitochondrial base editing to not only generate unique in vitro models to study these diseases, but also to functionally correct mitochondrial mutations in patient-derived cells for future therapeutic purposes.

Humans↗
PubMed2026

Fetal signatures in the 3D genome of iPSC-derived neurons and their implications for disease modeling.

Induced pluripotent stem cells (iPSCs) have revolutionized neuroscience, providing an approach to generate patient-specific neurons for modeling of neurological diseases. However, it remains unclear how closely iPSC-derived neurons replicate the chromatin architecture of authentic brain neurons. Here, we uniformly processed newly generated Hi-C data from iPSC-derived neurons and neurons isolated from the human postmortem brain, together with previously published data sets comprising 228 human and 89 mouse Hi-C and snm3C-seq samples from different cell subtypes. These data were merged into 96 high-coverage contact maps used to examine chromatin features ranging from chromatin compartments and topologically associating domains (TADs) to chromatin loops, Polycomb-mediated contacts, and frequently interacting regions (FIREs). We find that iPSC-derived neurons largely retain the chromatin state of undifferentiated cells and resemble fetal rather than mature neurons. iPSC-derived neurons exhibit unusually strong compartmentalization, an enrichment of developmental genes at TAD borders, and a marked reduction of long-range repressive Polycomb-mediated contacts that typically silence early fetal programs. Although immature, iPSC-derived neurons offer advantages for modeling interactions between disease-associated SNPs and target genes, as many psychiatric disorders have neurodevelopmental origins. Integrating iPSC-derived and postmortem neuronal data sets therefore provides complementary insights into the chromatin landscape underlying disease-associated interactions. Our study offers a valuable Hi-C resource for the community and provides a detailed comparison of chromatin architecture throughout neuronal maturation, underscoring its importance for validating neuronal models and providing a robust framework for future studies.

Journal Article↗
PubMed2025

Identification of Potential Therapeutic Agents for Type I Interferonopathy Using iPSC-Based Disease Modeling.

PURPOSE: Type I interferonopathy encompasses disorders marked by systemic inflammation and neurological involvement, arising from genetic mutations that result in the upregulation of type I IFN signaling through various mechanisms. Currently, therapeutic options are limited, and no standard therapy exists. This study aims to develop a strategy for identifying new therapeutic targets for type I interferonopathy using induced pluripotent stem cells (iPSCs). METHODS: The IFIH1 R779H variant was introduced into iPSCs through genome editing. RNA sequencing of iPSC-derived dendritic cells (DCs) was performed, and differentially expressed genes (DEGs) were identified. IFN-α secretion, reactive oxygen species (ROS), and mitochondrial oxygen consumption rate (OCR) were analyzed in iPSC-derived DCs. An in silico prediction of compounds binding to the OAS-like domain was conducted. Candidate compounds were evaluated for their ability to inhibit IFN secretion from IFIH1 R779H-mutated iPSC-derived DCs. RESULTS: Transcriptome analysis indicated upregulation of the IFN-related and metabolic pathways. IFIH1 R779H-mutated iPSC-derived DCs exhibited increased OCR and ROS generation, and blocking mitochondrial metabolism significantly reduced excessive IFN-α secretion. Among the DEGs, PML was upregulated, and targeting this gene with arsenic trioxide (ATO), a PML antagonist, suppressed IFN-α secretion from IFIH1 R779H-mutated iPSC-derived DCs. Additionally, bisantrene, phthalylsulfathiazole and ganaplacide were predicted to bind to the RNA binding groove of OAS-like domain of human OASL in silico, effectively inhibiting IFN-α secretion from IFIH1 R779H-mutated DCs. CONCLUSION: Our iPSC-based disease modeling and drug investigation approach provides a robust platform for validating the efficacy and toxicity of candidate therapeutic agents for rare and intractable human diseases such as type I interferonopathy.

Humans↗
PubMed1977

Pathogenesis of infection with Rickettsia rickettsii in the dog: a disease model for Rocky Mountain spotted fever.

Dogs inoculated with Rickettsia rickettsii developed a clinical syndrome ranging in severity from a mild febrile exanthema to death within six days after inoculation. The severity of the disease appeared to be dose-related, and the signs were comparable to R. rickettsii infection in humans on a clinical and hematological basis. Dogs were rickettsemic for 10 to 14 days after infection. In most animals the level of rickettsemia was greater than or equal to 10(2.5) guinea pig intraperitoneal 50% infectious doses (GPID50). Infected dogs responded serologically as determined by indirect fluorescent antibody methods and were protected when challenged six to 12 months later with 10(7.0) GPID50 of the homologous strain of R. rickettsii. The monocyte culture technique was successfully used for the detection of rickettsemia, and the results compared favorably with those obtained by the guinea pig inoculation method of isolation.

Animals↗
PubMed1979

[Organ zinc content in an experimental animal disease model: dystrophy-dependent changes in the liver and skeletal muscles and effects of a mineral substitute during the recovery phase].

The zinc content of the liver and the thigh muscle of the rat were measured by means of atomic absorption spectrophotometry under different conditions: standard diet, carbohydrate diet, an experimental dystrophy model and its recovery period. The influence of a parental mineral substitution on the whole body and the organ weight was studied. Carbohydrate diet caused a lower rise of the whole body weight, a decrease of the zinc content of the liver and an increase of the zinc content of the thigh muscle. In dystrophy model, the liver weight decreased to one fifth of the controls. The zinc concentration of the liver increased markedly, the zinc content of the whole liver is equal to that of control animals. The thigh muscle showed an increase of the zinc content, too. The parenteral mineral application had no effect upon the whole body weight and the organ weights. Little influences on the zinc content of the skeletal muscle were seen. The zinc content of parenchymatous organs varies markedly, and it is influenced by diets and disease. In the dystrophy model, zinc is concentrated in atrophic organs in order to protect the organism against zinc deficiency.

Animals↗
PubMed2025

Hierarchical Multi-Label Classification With Gene-Environment Interactions in Disease Modeling.

In biomedical studies, gene-environment (G-E) interactions have been demonstrated to have important implications for analyzing disease outcomes beyond the main G and main E effects. Many approaches have been developed for G-E interaction analysis, yielding important findings. However, hierarchical multi-label classification, which provides insightful information on disease outcomes, remains unexplored in G-E analysis literature. Moreover, unlabeled data are commonly observed in practical settings but omitted by many existing methods of hierarchical multi-label classification. In this study, we consider a semi-supervised scenario and develop a novel approach for the two-layer hierarchical response with G-E interactions. A two-step penalized estimation is then proposed using an efficient expectation-maximization (EM) algorithm. Simulation shows that it has superior performance in classification and feature selection. The analysis of The Cancer Genome Atlas (TCGA) data on lung cancer demonstrates the practical utility of the proposed method. Overall, this study can fill the important knowledge gap in G-E interaction analysis by providing a widely applicable framework for hierarchical multi-label classification of complex disease outcomes.

Humans↗
PubMed2025

Poly(ADP-ribose) Polymerase 1 Deficiency Attenuates Amyloid Pathology, Neurodegeneration, and Cognitive Decline in a Familial Alzheimer's Disease Model.

Poly(ADP-ribose) (PAR) polymerase-1 (PARP1) has been implicated in DNA damage responses and neuroinflammation in Alzheimer's disease (AD), yet its role in amyloid-β (Aβ) pathology remains unclear. Here, we show that PARP1 activation drives Aβ pathology and neurodegeneration. Using a sensitive ELISA, we observed significantly elevated PAR levels in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) and AD compared to controls. In vitro, oligomeric Aβ1-42 activated PARP1 and induced DNA damage, while genetic or pharmacological inhibition of PARP1 conferred neuroprotection. In vivo, PARP1 knockout in the 5XFAD mouse model of amyloidosis led to reduced amyloid plaque burden, preserved synaptic and neuronal integrity, attenuated glial activation and neuroinflammation, and rescued cognitive deficits. Mechanistically, PARP1 deficiency decreased amyloid precursor protein (APP) and BACE1 levels, altered γ-secretase complex composition, and enhanced Aβ degradation via neprilysin. These findings position PARP1 as a critical mediator of Aβ toxicity and neurodegeneration, suggesting its inhibition as a promising therapeutic strategy for AD.

Alzheimer’s disease↗
PubMed2026

CRISPR/Cas9-mediated editing of ERCC6 in iPSCs: A disease model for Cockayne Syndrome type B.

Cockayne Syndrome type B (CSB) is caused by mutations in the ERCC6 gene, which encodes a key protein involved in transcription-coupled nucleotide excision repair (TC-NER) and chromatin remodeling. Deficiency in CSB leads to defective transcriptional recovery after DNA damage, oxidative stress accumulation, and progressive neurodegeneration. In this work, we generated a CRISPR/Cas9-engineered human induced pluripotent stem cell (iPSC) line, IUFi004-A-12, carrying a homozygous mutation in ERCC6 causing a premature stop codon in its 10th exon. The modified iPSCs displayed normal morphology, expressed pluripotency markers, and differentiated into all three germ layers. This model enables mechanistic studies of CSB dysfunction and facilitates therapeutic development for Cockayne Syndrome.

Humans↗