Assessment of the effect of tricaine (MS-222)-induced anesthesia on brain-wide neuronal activity of zebrafish () larvae.

Fast and effective anesthesia is the key for refining many invasive procedures in fish and gaining reliable data. For fish as for all vertebrates, it is also required by European law to reduce pain, suffering, and distress to the unavoidable minimum in husbandry and experiments. The most often used substance to induce anesthesia in zebrafish is tricaine (MS-222).

Automatic classification of experimental models in biomedical literature to support searching for alternative methods to animal experiments.

Current animal protection laws require replacement of animal experiments with alternative methods, whenever such methods are suitable to reach the intended scientific objective. However, searching for alternative methods in the scientific literature is a time-consuming task that requires careful screening of an enormously large number of experimental biomedical publications. The identification of potentially relevant methods, e.

Current Methods to Investigate Nociception and Pain in Zebrafish.

Pain is an unpleasant, negative emotion and its debilitating effects are complex to manage. Mammalian models have long dominated research on nociception and pain, but there is increasing evidence for comparable processes in fish. The need to improve existing pain models for drug research and the obligation for 3R refinement of fish procedures facilitated the development of numerous new assays of nociception and pain in fish.

Dysregulated miR-125a promotes angiogenesis through enhanced glycolysis.

Background: Although neoangiogenesis is a hallmark of chronic inflammatory diseases such as inflammatory arthritis and many cancers, therapeutic agents targeting the vasculature remain elusive. Here we identified miR-125a as an important regulator of angiogenesis.

Methods: MiRNA levels were quantified in Psoriatic Arthritis (PsA) synovial-tissue by RT-PCR and compared to macroscopic synovial vascularity.

Orthogonal Drug Pooling Enhances Phenotype-Based Discovery of Ocular Antiangiogenic Drugs in Zebrafish Larvae.

Unbiased screening of large randomized chemical libraries is a powerful tool to find new drugs and targets. However, forward chemical screens in zebrafish can be time consuming and usually >99% of test compounds have no significant effect on the desired phenotype. Here, we sought to find bioactive drugs more efficiently and to comply with the 3R principles of replacement, reduction, and refinement of animals in research.

Erk5 activation elicits a vasoprotective endothelial phenotype via induction of Kruppel-like factor 4 (KLF4).

The MEK5/Erk5 MAPK cascade has recently been implicated in the regulation of endothelial integrity and represents a candidate pathway mediating the beneficial effects of laminar flow, a major factor preventing vascular dysfunction and disease. Here we expressed a constitutively active mutant of MEK5 (MEK5D) to study the transcriptional and functional responses to Erk5 activation in human primary endothelial cells. We provide evidence that constitutive Erk5 activation elicits an overall protective phenotype characterized by increased apoptosis resistance and a decreased angiogenic, migratory, and inflammatory potential.

MEK5/ERK5 signaling modulates endothelial cell migration and focal contact turnover.

The formation of new blood vessels from pre-existing ones requires highly coordinated restructuring of endothelial cells (EC) and the surrounding extracellular matrix. Directed EC migration is a central step in this process and depends on cellular signaling cascades that initiate and control the structural rearrangements. On the basis of earlier findings that ERK5 deficiency in mouse EC results in massive defects in vessel architecture, we focused on the impact of the MEK5/ERK5 signaling pathway on EC migration.

Wnt2 acts as an angiogenic growth factor for non-sinusoidal endothelial cells and inhibits expression of stanniocalcin-1.

Recently, we have shown that Wnt2 is an autocrine growth and differentiation factor for hepatic sinusoidal endothelial cells. As Wnt signaling has become increasingly important in vascular development and cancer, we analyzed Wnt signaling in non-sinusoidal endothelial cells of different vascular origin (HUVEC, HUAEC, HMVEC-LLy). Upon screening the multiple components of the Wnt pathway, we demonstrated lack of Wnt2 expression, but presence of Frizzled-4, one of its receptors, in cultured non-sinusoidal endothelial cells.