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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↗
PubMed1990

The new disease model of alcoholism.

The new biopsychosocial disease model of alcoholism is examined from the perspective of recent biologic research. Studies of animal and human genetic predispositions suggest the presence of genetic influences over drinking behavior as well as biologic risk factors related to deficiencies in various neurochemicals. Ethanol affects the fluidity of cell membrane lipids, eventually causing membrane dysfunction. It also adversely affects the activity of two enzymes, monoamine oxidase and adenylate cyclase, that have important functions in the information processing system of the brain. Research on condensation products formed in the brain after alcohol consumption has provided clues to the development of alcoholism, but many questions remain unanswered. Alcoholism is clearly a multidimensional phenomenon in which biologic, psychological, and sociocultural factors interact to produce illness.

Alcoholism↗
PubMed1991

MERRF: a model disease for understanding the principles of mitochondrial genetics.

The principles of mitochondrial genetics have evolved over the past 20 years. Careful identification of large pedigrees that were consistent with maternal inheritance has permitted detailed clinical and genetic investigations. Myoclonic epilepsy and ragged-red fiber (MERRF) disease has been a model disease for the application of these principles. MERRF is caused by an A to G mutation of the mitochondrial tRNA(Lys) at position 8344. The mutation is maternally inherited and heteroplasmic. Disease manifestations are dependent on replicative segregation of mutant and wild type mitochondrial DNAs and on the threshold effect. Characterization of the clinical, physiological, biochemical, and genetic manifestations of this disease has provided a better understanding of how to diagnose and manage oxidative phosphorylation diseases which are caused by mutations in the mitochondrial DNA.

Base Sequence↗
PubMed1992

Curative factors in alcohol and drug treatment: behavioral and disease model perspectives.

Unlike the general psychotherapy field which has been subjected to extensive process analysis, there are no systematic studies of treatment processes in the alcohol and drug treatment literature. As a necessary first step to study treatment process, the alcohol and drug literature was culled for references to treatment processes. Thirty-five separate processes were identified and were broadly categorized as either disease model, behavioral or general psychotherapy processes. A national survey of treatment expert's views on treatment processes was conducted to determine whether certain processes would be considered as most important in the treatment of alcohol or drug problems. Results of this survey indicate that experts tend to rate certain processes as most important in the resolution of alcohol and drug problems. Results suggest that it is possible to identify core disease model and behavioral treatment processes. These processes might be used to assess the relative effectiveness of each therapeutic approach. Finally, results indicated that while disease model and behavioral experts tended to differ strongly on their ratings of the importance of some processes, there seems to be a trend toward integrating behavioral processes into a traditional disease model framework. The use of these results in constructing an instrument to measure processes used in alcohol and drug treatment is discussed.

Adult↗
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↗
PubMed1992

Hemagglutination and graft-versus-host disease in the severe combined immunodeficiency mouse lymphoproliferative disease model.

In the course of evaluating the severe combined immunodeficiency mouse-human peripheral blood lymphocyte (SCID-PBL) model of lymphoproliferative disease, we noted hemagglutination occurring in peripheral blood smears of mice with serum human immunoglobulin levels greater than 1.0 mg/ml. The hemagglutinating process was mediated by human anti-mouse red cell antibodies of the IgM class, peaked at five to seven weeks post-transfer of 5 to 7 x 10(7) human PBL and was generally self limiting. However, death resulted in some mice when serum immunoglobulin levels were greater than 3.0 mg/ml. The most severely affected mice had hemagglutination induced congestion of liver, lungs and spleen. Several mice also had lesions consistent with graft-versus-host disease (GVHD) including focal hepatic necrosis and destruction of mouse splenic hematopoietic elements. The lesions associated with hemagglutination and GVHD in SCID-PBL mice are distinct from those associated with EBV-induced lymphoproliferation. Recognition of these pathologic processes are required for a thorough understanding of the SCID-PBL model.

Animals↗
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↗
PubMed1992

Left ventricular contractility and energetic cost in disease models--an approach from the pressure-volume diagram.

Left ventricular contractility and the energetic cost of contraction were assessed in various disease models in experimental animals utilizing frameworks of Emax (left ventricular contractility index) and pressure-volume area (PVA, a measure of total left ventricular mechanical energy expenditure) derived from the pressure-volume (P-V) diagram. Under various contractile conditions, PVA linearly correlates with myocardial oxygen consumption per beat (VO2) in a load-independent manner. The reciprocal of the slope of the linear VO2-PVA relation indicates "contractile efficiency" (the energy transduction efficiency from oxygen to total mechanical energy). It was similar between dog and rabbit hearts (about 40%) and was not significantly affected by enhanced contractility with calcium, epinephrine, or cardiac cooling, or by depressed contractility with propranolol, decreased coronary perfusion pressure, or stunned myocardium. However, in thyrotoxic rabbit hearts contractile efficiency was significantly depressed compared to normal hearts. On the other hand, the VO2 intercept of the VO2-PVA relation (PVA-independent VO2), which reflects VO2 for non-mechanical activities such as excitation-contraction coupling and basal metabolism, positively correlates with Emax. Therefore, the ratio of an increase in PVA-independent VO2 to an increase in Emax indicates "oxygen cost of contractility". Oxygen cost of contractility was higher in stunned myocardium than in normal hearts, suggesting that the energy cost of calcium handling is elevated in stunned myocardium. Thus, using the frameworks of Emax and PVA, we can interconnect cardiac mechanics and energetics. Further, using the concepts of contractile efficiency and oxygen cost of contractility, we can approach the pathogenesis of variously altered contractile conditions.

Animals↗
PubMed1991

A discrete-time communicable disease model with a stochastic contact rate for nonhomogeneous populations.

A discrete-time communicable disease model with a stochastic contact rate for nonhomogeneous populations is described which is capable of simulating the irregular incidence patterns seen in many communicable diseases. The epidemic curve for these contagious diseases is typically characterized by epidemics of varying intensity separated by variable time intervals. The compartmental model is an extension to the Reed-Frost theory with age-specific stochastic contact rates. The population is partitioned into age constant groups and is closed; the births flowing into the first age group equals the deaths from all age groups. The population in each age group is subdivided into four states that characterize the course of an infection: susceptible, incubation, infectious, and immune. The incubation and infectious states are divided further depending on the length of the time period and the statistics of the condition. The age specific contact rates are random variables with a seasonal variation and a population specified density function. An example is presented in which all parameters and distributions of the model are estimated for measles in the city of Baltimore, Maryland for the years 1900 through 1917. The computer calculated epidemic curves adequately describe the incidence pattern of the data with no significant differences noted.

Adolescent↗
PubMed1990

[Transgenic mice as disease models].

The methods used for making transgenic mice such as DNA microinjection in pronuclei, transformation of embryonic stem cells and production of chimeras, infection by retroviral vectors and sperm cells as carriers for foreign DNA are reported. Furthermore some characteristics of transgenic mice are mentioned, in particular factors influencing integration and expression of gene constructs. Different kinds of disease models using transgenic mice are available. This has been achieved by insertional mutagenesis, dominant negative mutations, changes caused by overexpression of transgenes, gene ablation, targeted mutation, and transfer of oncogenes. The importance of ongoing research in transgenic animals is emphasized.

Animals↗
PubMed1990

Effect of exogenous surfactant on the development of bronchopulmonary dysplasia in a baboon hyaline membrane disease model.

To test the effect of exogenous surfactant on the evolution of histopathologic changes of bronchopulmonary dysplasia (BPD), we conducted a study in a premature baboon hyaline membrane disease model. One hundred mg/kg bovine surfactant sonicated in saline or 3 ml/kg saline placebo was instilled via the trachea at about 10 min of age. The clinical status and physiologic changes were monitored for 9 days, and pulmonary histopathology was evaluated after death. Compared to the control, the surfactant-treated animals showed a significant improvement in arterial/alveolar oxygen ratio and pulmonary compliance, facilitating rapid weaning from assisted ventilation. Lung histology revealed that pulmonary parenchyma expanded 70% to 95% without features of early BPD. Dysplastic maturation, air trapping, or cellular atypia was not seen. In contrast, lung histology in the control group revealed alveolar expansion less than or equal to 50%, basal cell hyperplasia in the bronchial and bronchiolar epithelium, dysplastic maturation with cellular atypia, extensive epithelial erosion, and type II cell hyperplasia, all features of early BPD. The results of this study suggest that in the premature baboon model, exogenous surfactant therapy improves pulmonary functional abnormalities and lessens the histologic features of BPD, perhaps because of rapid weaning and reduced barotrauma.

Animals↗
PubMedDate not supplied

Controlled drinking, treatment effectiveness, and the disease model of addiction: a commentary on the ideological wishes of Stanton Peele.

Despite a long history of extravagant claims followed by sobering discomfirmations, advocates of controlled drinking continue to promote nonabstinent treatment goals and procedures for alcoholics. Recent claims by Stanton Peele in favor of controlled drinking are examined critically in the context of a continuing debate concerning empirical studies of nonabstinent treatment goals, treatment effectiveness, and inpatient versus out-patient treatment of alcoholism. Peele's views concerning "conventional disease-based alcoholism treatment," controlled drinking, and "the disease model" are shown to be based largely on inadequate scholarship, misrepresentations of the literature, inappropriate comparisons, unwarranted generalizations, and straw-man arguments.

Alcohol Drinking↗