LncRNAs and the Control of Oncogenic Signaling
Abstract
An increasing amount of evidence points to key roles for noncoding RNAs in gene expression regulation and cell function. Similar to smaller species, long noncoding RNAs (lncRNAs) are involved in a myriad of molecular pathways, impacting on and fine-tuning proliferative and differentiating cellular programs. Specifically in tumorigenesis, several lncRNAs have been shown to display growth enhancing or arrest properties and can therefore be considered as true oncogenes or tumor suppressor genes. This review focuses on the latest findings in the noncoding field regarding transcripts with crucial role...
Source: Current Pathobiology Reports - July 7, 2015 Category: Laboratory Medicine Source Type: research
Mouse Models as Predictors of Human Responses: Evolutionary Medicine
Abstract
Mice offer a number of advantages and are extensively used to model human diseases and drug responses. Selective breeding and genetic manipulation of mice have made many different genotypes and phenotypes available for research. However, in many cases, mouse models have failed to be predictive. Important sources of the prediction problem have been the failure to consider the evolutionary basis for species differences, especially in drug metabolism, and disease definitions that do not reflect the complexity of gene expression underlying disease phenotypes. Incorporating evolutionary insights into ...
Source: Current Pathobiology Reports - July 7, 2015 Category: Laboratory Medicine Source Type: research
Phosphodiesterase Type 5 as a Candidate Therapeutic Target in Cancers
Abstract
The global burden of cancer is largely increasing because of population aging and growth alongside an adoption of cancer-causing lifestyle choices. The majority of cancers can be treated, and certain can be cured, depending on their type, location, and stage. Although conventional therapies have changed the natural history of the disease, many tumors exhibit drug resistance and severe adverse effects remain major therapeutic hurdles. On the other hand, clinical trials and meta-analyses have demonstrated that multi-modality treatments may improve patient outcome and have acceptable tolerability pr...
Source: Current Pathobiology Reports - July 1, 2015 Category: Laboratory Medicine Source Type: research
Zebrafish Models of Kidney Damage and Repair
Abstract
The vertebrate kidney possesses the capacity to repair damaged nephrons, and this potential is conserved regardless of the complexity of species-specific kidneys. However, many aquatic vertebrates possess the ability to not only repair existing nephrons, but also generate new nephrons after injury. Adult zebrafish have the ability to recover from acute renal injury not only by replacing lost injured epithelial cells of endogenous nephrons, but by also generating de novo nephrons. This strong regeneration potential, along with other unique characteristics such as the high degree of genetic conserv...
Source: Current Pathobiology Reports - April 10, 2015 Category: Laboratory Medicine Source Type: research
Aging Lesions: Background Versus Phenotype
This article aims to raise awareness of the range of these background (incidental) lesions that may be seen in mice particularly as they age and that need to be differentiated from specific phenotypic changes. Experimental factors which can influence pathology and can result in artifacts are also discussed. (Source: Current Pathobiology Reports)
Source: Current Pathobiology Reports - April 10, 2015 Category: Laboratory Medicine Source Type: research
Zebrafish Renal Pathology: Emerging Models of Acute Kidney Injury
Abstract
The renal system is vital to maintain homeostasis in the body, where the kidneys contain nephron functional units that remove metabolic waste from the bloodstream, regulate fluids, and balance electrolytes. Severe organ damage from toxins or ischemia that occurs abruptly can cause acute kidney injury (AKI) in which there is a rapid, life-threatening loss of these activities. Humans have a limited but poorly understood ability to regenerate damaged nephrons after AKI. However, researchers studying AKI in vertebrate animal models such as mammals, and more recently the zebrafish, have documented rob...
Source: Current Pathobiology Reports - April 8, 2015 Category: Laboratory Medicine Source Type: research
Key Fibrogenic Signaling
Abstract
Fibrosis is defined as an excessive accumulation of extracellular matrix components that lead to the destruction of organ architecture and impairment of organ function. Moreover, fibrosis is an intricate process attributable to a variety of interlaced fibrogenic signals and intrinsic mechanisms of activation of myofibroblasts. Being the dominant matrix-producing cells in organ fibrosis, myofibroblasts may be differentiated from various types of precursor cells. Identification of the signal pathways that play a key role in the pathogenesis of fibrotic diseases may suggest potential therapeutic tar...
Source: Current Pathobiology Reports - April 4, 2015 Category: Laboratory Medicine Source Type: research
Infection, Inflammation and Healing in Zebrafish: Intestinal Inflammation
Abstract
Inflammatory bowel diseases (IBD), which include Crohn’s disease and ulcerative colitis, contribute to significant morbidity and mortality globally. Despite an increase in incidence, IBD onset is still poorly understood. Mouse models of IBD recapitulate several aspects of human disease, but limited accessibility for live imaging and the lack of forward genetics highlight the need for new model systems for disease onset characterization. Zebrafish represent a powerful platform to model IBD using forward and reverse genetics, live imaging of transgenic lines, and physiological assays. In this rev...
Source: Current Pathobiology Reports - April 4, 2015 Category: Laboratory Medicine Source Type: research
The Xenopus Embryo: An Ideal Model System to Study Human Ciliopathies
Abstract
Over the past two decades or so, our understanding of gene function has come primarily from animal model organisms. In cases, when human disease alleles were found in developmental key genes, the translational aspect was deduced from the experimental animal model data. With the rapid improvement of sequencing technologies and data processing, we envisage that rare genetic disease alleles will be identified quickly and easily. As a consequence, experiments in animal models will be necessary to elucidate disease mechanisms, resulting in a workflow from the disease allele to experimentation in anima...
Source: Current Pathobiology Reports - April 3, 2015 Category: Laboratory Medicine Source Type: research
Modeling Disorders of Blood Coagulation in the Zebrafish
Abstract
Hemostasis, the process of blood clot formation and resolution in response to vascular injury, and thrombosis, the dysregulation of hemostasis leading to pathological clot formation, are widely studied. However, the genetic variability in hemostatic and thrombotic disorders is incompletely understood, suggesting that novel mediators have yet to be uncovered. The zebrafish is developing into a powerful in vivo model to study hemostasis, and its features as a model organism are well suited to (a) develop high-throughput screens to identify novel mediators of hemostasis and thrombosis, (b) validate ...
Source: Current Pathobiology Reports - April 3, 2015 Category: Laboratory Medicine Source Type: research
Xenopus as a Model for GI/Pancreas Disease
Abstract
Diseases affecting endodermal organs like the pancreas, lung, and gastrointestinal tract have a substantial impact on human welfare. Since many of these are congenital defects that arise as a result of defects during development, broad efforts are focused on understanding the development of these organs so as to better identify risk factors, disease mechanisms, and therapeutic targets. Studies implementing model systems, like the amphibian Xenopus, have contributed immensely to our understanding of signaling pathways (e.g., Wnt, FGF, BMP, RA) and gene regulation (e.g., hhex, ptf1a, ngn3) that und...
Source: Current Pathobiology Reports - April 2, 2015 Category: Laboratory Medicine Source Type: research
Finding Order in Human Neurological Disorder Using a Tadpole
Abstract
The Xenopus tadpole has been used for decades to study neural development. Every stage of neural development, from neural induction and neurogenesis to axon guidance and circuit refinement has been described in this particular model. This review discusses the unique experimental attributes of the Xenopus tadpole that make it a powerful model for studying how neural circuits form and function, and highlights the especially innovative ways this model is currently being used to identify and characterize the pathophysiology associated with neurological disorders. Focus is on three key stages of neura...
Source: Current Pathobiology Reports - April 2, 2015 Category: Laboratory Medicine Source Type: research
Systems Biology Approaches Applied to Regenerative Medicine
Abstract
Systems biology is the creation of theoretical and mathematical models for the study of biological systems, as an engine for hypothesis generation and to provide context to experimental data. It is underpinned by the collection and analysis of complex datasets from different biological systems, including global gene, RNA, protein and metabolite profiles. Regenerative medicine seeks to replace or repair tissues with compromised function (for example, through injury, deficiency or pathology), in order to improve their functionality. In this paper, we will address the application of systems biology ...
Source: Current Pathobiology Reports - February 10, 2015 Category: Laboratory Medicine Source Type: research
From Human-Induced Pluripotent Stem Cells to Liver Disease Modeling: A Focus on Dyslipidemia
Abstract
Since the reprogramming of human somatic cells into induced pluripotent stem cells (hiPSCs) became a reality, numerous advances have been made for the reprogramming process itself, cell differentiation and disease modeling. While differentiation procedures of hiPSCs into hepatocyte-like cells are under continuous investigations in order to generate fully mature and functional hepatocytes, current models already showed great promises in terms of modeling liver pathologies including metabolic diseases. This review provides an overview of the reprogramming, hepatic differentiation, and application a...
Source: Current Pathobiology Reports - February 8, 2015 Category: Laboratory Medicine Source Type: research
Placenta as a Source of Stem Cells for Regenerative Medicine
Abstract
The development of effective cell transplantation therapies is currently the focus of biomedical research worldwide, and numerous cell types and sources have been explored for applications in regenerative medicine. The placenta is a unique organ of fetomaternal origin that plays an important role in fetal development, and multiple types of placenta-derived stem cells show great promise for application in regenerative medicine. This review concisely summarizes the recent proceedings on the characterization, biological properties, and applications of mesenchymal stem cells that have been isolated f...
Source: Current Pathobiology Reports - February 3, 2015 Category: Laboratory Medicine Source Type: research
