scholarly journals Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Athina Georgiadou ◽  
Claire Dunican ◽  
Pablo Soro-Barrio ◽  
Hyun Jae Lee ◽  
Myrsini Kaforou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Animal Models ◽  
Mouse Models ◽  
Clinical Manifestations ◽  
Plasmodium Yoelii ◽  
Biological Mechanisms ◽  
Microvascular Pathology ◽  
High Parasite ◽  
Comparative Transcriptomic Analysis ◽  
Selection Of

Recent initiatives to improve translation of findings from animal models to human disease have focussed on reproducibility but quantifying the relevance of animal models remains a challenge. Here, we use comparative transcriptomics of blood to evaluate the systemic host response and its concordance between humans with different clinical manifestations of malaria and five commonly used mouse models. Plasmodium yoelii 17XL infection of mice most closely reproduces the profile of gene expression changes seen in the major human severe malaria syndromes, accompanied by high parasite biomass, severe anemia, hyperlactatemia, and cerebral microvascular pathology. However, there is also considerable discordance of changes in gene expression between the different host species and across all models, indicating that the relevance of biological mechanisms of interest in each model should be assessed before conducting experiments. These data will aid the selection of appropriate models for translational malaria research, and the approach is generalizable to other disease models.

scholarly journals Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria

2021 ◽  
Author(s):  
Athina Georgiadou ◽  
Claire Dunican ◽  
Pablo Soro-Barrio ◽  
Hyun Jae Lee ◽  
Myrsini Kaforou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Animal Models ◽  
Mouse Models ◽  
Clinical Manifestations ◽  
Plasmodium Yoelii ◽  
Microvascular Pathology ◽  
High Parasite ◽  
Comparative Transcriptomic Analysis ◽  
Plasmodium Yoelii 17Xl ◽  
Selection Of

Recent initiatives to improve translation of findings from animal models to human disease have focussed on reproducibility but quantifying the relevance of animal models remains a challenge. Here we use comparative transcriptomics of blood to evaluate the systemic host response and its concordance between humans with different clinical manifestations of malaria and five commonly used mouse models. Plasmodium yoelii 17XL infection of mice most closely reproduces the profile of gene expression changes seen in the major human severe malaria syndromes, accompanied by high parasite biomass, severe anemia, hyperlactatemia, and cerebral microvascular pathology. However, there is also considerable discordance of changes in gene expression between species and across all models, indicating that the relevance of biological mechanisms of interest in each model should be assessed before conducting experiments. Our data will aid selection of appropriate models for translational malaria research, and the approach is generalizable to other disease models.

scholarly journals Models of multiple system atrophy

2019 ◽  
Vol 51 (11) ◽  
pp. 1-10 ◽  
Author(s):  
He-Jin Lee ◽  
Diadem Ricarte ◽  
Darlene Ortiz ◽  
Seung-Jae Lee
Keyword(s):  
Animal Models ◽  
Multiple System Atrophy ◽  
Mouse Models ◽  
Clinical Manifestations ◽  
Lewy Bodies ◽  
Model Systems ◽  
Future Research ◽  
Cytoplasmic Inclusions ◽  
Cellular Models ◽  
Brain Extracts

AbstractMultiple system atrophy (MSA) is a neurodegenerative disease with diverse clinical manifestations, including parkinsonism, cerebellar syndrome, and autonomic failure. Pathologically, MSA is characterized by glial cytoplasmic inclusions in oligodendrocytes, which contain fibrillary forms of α-synuclein. MSA is categorized as one of the α-synucleinopathy, and α-synuclein aggregation is thought to be the culprit of the disease pathogenesis. Studies on MSA pathogenesis are scarce relative to studies on the pathogenesis of other synucleinopathies, such as Parkinson’s disease and dementia with Lewy bodies. However, recent developments in cellular and animal models of MSA, especially α-synuclein transgenic models, have driven advancements in research on this disease. Here, we review the currently available models of MSA, which include toxicant-induced animal models, α-synuclein-overexpressing cellular models, and mouse models that express α-synuclein specifically in oligodendrocytes through cell type-specific promoters. We will also discuss the results of studies in recently developed transmission mouse models, into which MSA brain extracts were intracerebrally injected. By reviewing the findings obtained from these model systems, we will discuss what we have learned about the disease and describe the strengths and limitations of the models, thereby ultimately providing direction for the design of better models and future research.

scholarly journals Genomic responses in mouse models greatly mimic human inflammatory diseases

2014 ◽  
Vol 112 (4) ◽  
pp. 1167-1172 ◽  
Author(s):  
Keizo Takao ◽  
Tsuyoshi Miyakawa
Keyword(s):  
Gene Expression ◽  
Animal Models ◽  
Mouse Models ◽  
Inflammatory Diseases ◽  
Meta Analysis ◽  
Expression Patterns ◽  
Rank Correlation ◽  
Expression Levels ◽  
Spearman’S Rank Correlation ◽  
Spearman’S Rank Correlation Coefficient

The use of mice as animal models has long been considered essential in modern biomedical research, but the role of mouse models in research was challenged by a recent report that genomic responses in mouse models poorly mimic human inflammatory diseases. Here we reevaluated the same gene expression datasets used in the previous study by focusing on genes whose expression levels were significantly changed in both humans and mice. Contrary to the previous findings, the gene expression levels in the mouse models showed extraordinarily significant correlations with those of the human conditions (Spearman’s rank correlation coefficient: 0.43–0.68; genes changed in the same direction: 77–93%; P = 6.5 × 10−11 to 1.2 × 10−35). Moreover, meta-analysis of those datasets revealed a number of pathways/biogroups commonly regulated by multiple conditions in humans and mice. These findings demonstrate that gene expression patterns in mouse models closely recapitulate those in human inflammatory conditions and strongly argue for the utility of mice as animal models of human disorders.

scholarly journals The Tree Shrew as a Model for Cancer Research

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Lu ◽  
Hongmei Peng ◽  
Liping Zhong ◽  
Pan Wu ◽  
Jian He ◽  
...  
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Tree Shrew ◽  
Clinical Manifestations ◽  
Animal Disease ◽  
Tree Shrews ◽  
Animal Disease Models ◽  
Conserved Genes ◽  
Tumor Research ◽  
Selection Of

Animal disease models are necessary in medical research, and an appropriate animal model is of great importance for studies about the prevention or treatment of cancer. The most important thing in the selection of animal models is to consider the similarity between animals and humans. The tree shrew (Tupaia belangeri) is a squirrel-like mammal which placed in the order Scandentia. Whole-genome sequencing has revealed that tree shrews are extremely similar to primate and humans than to rodents, with many highly conserved genes, which makes the data from studies that use tree shrews as models more convincing and the research outcomes more easily translatable. In tumor research, tree shrews are often used as animal models for hepatic and mammary cancers. As research has progressed, other types of tree shrew tumor models have been developed and exhibit clinical manifestations similar to those of humans. Combining the advantages of both rodents and primates, the tree shrew is expected to be the most powerful animal model for studying tumors.

scholarly journals Biological Heterogeneity

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 854-855
Author(s):  
Blanka Rogina
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Animal Models ◽  
Clinical Manifestations ◽  
Clonal Expansion ◽  
Biological Aging ◽  
Significant Heterogeneity ◽  
Qualitative And Quantitative ◽  
Biological Heterogeneity ◽  
Quantitative Changes

Abstract Studies of aging in invertebrates, mammalian animal models and humans have demonstrated increasing heterogeneity with aging in terms of varied facets of biological aging. In addition to growing heterogeneity, aging is also associated with qualitative and quantitative changes involving DNA methylation captured in epigenetic clocks of aging which seek to predict chronological and biological aging. Increased heterogeneity with aging is also evident in terms of posttranslational histone modification, gene expression, somatic clonal expansion, and increased degree of tissue mosaicism. Senescent cells accumulating with aging demonstrate significant heterogeneity. For example, while most studies targeting senescent cells have focused on cells expressing p16 (CDKN2A), not all p16-positive cells are senescent and not all senescent cells express p16. Further studies are needed to better define heterogeneity involving other hallmarks of aging and to also explore associations between heterogeneity involving these biological measures with clinical manifestations or outcomes.

HIF1-α-Mediated Gene Expression Induced by Vitamin B1 Deficiency

2013 ◽  
Vol 83 (3) ◽  
pp. 188-197 ◽  
Author(s):  
Rebecca L. Sweet ◽  
Jason A. Zastre
Keyword(s):  
Gene Expression ◽  
Thiamine Deficiency ◽  
Glucose Transporter ◽  
Neuroblastoma Cell ◽  
Hypoxia Inducible Factor ◽  
Clinical Manifestations ◽  
Vitamin B1 ◽  
Low Oxygen ◽  
Glucose Transporter 1 ◽  
Metabolic Intermediates

It is well established that thiamine deficiency results in an excess of metabolic intermediates such as lactate and pyruvate, which is likely due to insufficient levels of cofactor for the function of thiamine-dependent enzymes. When in excess, both pyruvate and lactate can increase the stabilization of the hypoxia-inducible factor 1-alpha (HIF-1α) transcription factor, resulting in the trans-activation of HIF-1α regulated genes independent of low oxygen, termed pseudo-hypoxia. Therefore, the resulting dysfunction in cellular metabolism and accumulation of pyruvate and lactate during thiamine deficiency may facilitate a pseudo-hypoxic state. In order to investigate the possibility of a transcriptional relationship between hypoxia and thiamine deficiency, we measured alterations in metabolic intermediates, HIF-1α stabilization, and gene expression. We found an increase in intracellular pyruvate and extracellular lactate levels after thiamine deficiency exposure to the neuroblastoma cell line SK-N-BE. Similar to cells exposed to hypoxia, there was a corresponding increase in HIF-1α stabilization and activation of target gene expression during thiamine deficiency, including glucose transporter-1 (GLUT1), vascular endothelial growth factor (VEGF), and aldolase A. Both hypoxia and thiamine deficiency exposure resulted in an increase in the expression of the thiamine transporter SLC19A3. These results indicate thiamine deficiency induces HIF-1α-mediated gene expression similar to that observed in hypoxic stress, and may provide evidence for a central transcriptional response associated with the clinical manifestations of thiamine deficiency.

Use of photodynamic therapy for photodamage skin (review of literature)

2019 ◽  
Vol 1 (7) ◽  
pp. 19-23
Author(s):  
S. I. Surkichin ◽  
N. V. Gryazeva ◽  
L. S. Kholupova ◽  
N. V. Bochkova
Keyword(s):  
Photodynamic Therapy ◽  
Comparative Evaluation ◽  
Clinical Manifestations ◽  
Light Sources ◽  
Review Of Literature ◽  
Photosensitizing Agents ◽  
Selection Of

The article provides an overview of the use of photodynamic therapy for photodamage of the skin. The causes, pathogenesis and clinical manifestations of skin photodamage are considered. The definition, principle of action of photodynamic therapy, including the sources of light used, the classification of photosensitizers and their main characteristics are given. Analyzed studies that show the effectiveness and comparative evaluation in the selection of various light sources and photosensitizing agents for photodynamic therapy in patients with clinical manifestations of photodamage.

СОВРЕМЕННЫЕ ПОДХОДЫ К ДИАГНОСТИКЕ И ЛЕЧЕНИЮ АНГИООТЕКОВ В ПЕДИАТРИИ

2019 ◽  
Author(s):  
A.R. Denisova ◽  
A.N. Pampura
Keyword(s):  
Clinical Manifestations ◽  
Personalized Therapy ◽  
Diagnostics And Therapy ◽  
Selection Of

Ангиоотеки довольно часто встречаются в детском возрасте. Эффективность ведения детей с ангиоотеками определяется пониманием патогенеза заболевания и подбором персонифицированной терапии. В статье представлены сведения о классификации, клинических проявлениях, диагностике и терапии как брадикинин-, так и гистаминергических ангиоотеков.Angioedema often occurs in childhood. The effectiveness of the management of children with angioedema is determined by understanding the pathogenesis of the disease and the selection of personalized therapy. This article provides information on the classification, clinical manifestations, diagnostics and therapy of both bradykinin and histaminergic angioedema.

Sign in / Sign up

Export Citation Format

Share Document