scholarly journals Introduction to Focus Issue: Dynamical disease: A translational approach

2021 ◽  
Vol 31 (6) ◽  
pp. 060401
Author(s):  
Jacques Bélair ◽  
Fahima Nekka ◽  
John G. Milton
Keyword(s):  
Dynamical Disease ◽  
Translational Approach

Mice selected for extremes in stress reactivity reveal key endophenotypes of major depression – A translational approach

2015 ◽  
Vol 122 (03) ◽  
Author(s):  
JM Heinzmann ◽  
S Kloiber ◽  
G Ebling Mattos ◽  
M Bielohuby ◽  
MV Schmidt ◽  
...  
Keyword(s):  
Major Depression ◽  
Stress Reactivity ◽  
Translational Approach

scholarly journals Clobetasol promotes neuromuscular plasticity in mice after motoneuronal loss via sonic hedgehog signaling, immunomodulation and metabolic rebalancing

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Nunzio Vicario ◽  
Federica M. Spitale ◽  
Daniele Tibullo ◽  
Cesarina Giallongo ◽  
Angela M. Amorini ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Neural Regeneration ◽  
Metabolic Effects ◽  
Motor Impairments ◽  
Sonic Hedgehog Signaling ◽  
Neuroprotective Effects ◽  
Promising Target ◽  
Translational Approach ◽  
Lateral Sclerosis

AbstractMotoneuronal loss is the main feature of amyotrophic lateral sclerosis, although pathogenesis is extremely complex involving both neural and muscle cells. In order to translationally engage the sonic hedgehog pathway, which is a promising target for neural regeneration, recent studies have reported on the neuroprotective effects of clobetasol, an FDA-approved glucocorticoid, able to activate this pathway via smoothened. Herein we sought to examine functional, cellular, and metabolic effects of clobetasol in a neurotoxic mouse model of spinal motoneuronal loss. We found that clobetasol reduces muscle denervation and motor impairments in part by restoring sonic hedgehog signaling and supporting spinal plasticity. These effects were coupled with reduced pro-inflammatory microglia and reactive astrogliosis, reduced muscle atrophy, and support of mitochondrial integrity and metabolism. Our results suggest that clobetasol stimulates a series of compensatory processes and therefore represents a translational approach for intractable denervating and neurodegenerative disorders.

scholarly journals Personalized medicine for reconstruction of critical-size bone defects – a translational approach with customizable vascularized bone tissue

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Annika Kengelbach-Weigand ◽  
Carolina Thielen ◽  
Tobias Bäuerle ◽  
Rebekka Götzl ◽  
Thomas Gerber ◽  
...  
Keyword(s):  
Personalized Medicine ◽  
Large Scale ◽  
Critical Size ◽  
Therapeutic Option ◽  
Living Organism ◽  
Bone Defects ◽  
Sheep Model ◽  
Simple Alternative ◽  
Translational Approach ◽  
Near Future

AbstractTissue engineering principles allow the generation of functional tissues for biomedical applications. Reconstruction of large-scale bone defects with tissue-engineered bone has still not entered the clinical routine. In the present study, a bone substitute in combination with mesenchymal stem cells (MSC) and endothelial progenitor cells (EPC) with or without growth factors BMP-2 and VEGF-A was prevascularized by an arteriovenous (AV) loop and transplanted into a critical-size tibia defect in the sheep model. With 3D imaging and immunohistochemistry, we could show that this approach is a feasible and simple alternative to the current clinical therapeutic option. This study serves as proof of concept for using large-scale transplantable, vascularized, and customizable bone, generated in a living organism for the reconstruction of load-bearing bone defects, individually tailored to the patient’s needs. With this approach in personalized medicine for the reconstruction of critical-size bone defects, regeneration of parts of the human body will become possible in the near future.

Ethical, Legal and Regulatory Issues of Paediatric Translational Research. Call for an Adequate Model of Governance

2020 ◽  
Vol 27 (3) ◽  
pp. 213-231
Author(s):  
Annagrazia Altavilla ◽  
Viviana Giannuzzi ◽  
Mariangela Lupo ◽  
Donato Bonifazi ◽  
Adriana Ceci
Keyword(s):  
Translational Research ◽  
Research Infrastructure ◽  
Paediatric Research ◽  
Adequate Model ◽  
Regulatory Issues ◽  
Societal Issues ◽  
Translational Approach ◽  
Legal Frameworks ◽  
Ethical Oversight ◽  
Paediatric Medicines

Abstract The lack of paediatric medicines, including innovative and advanced ones, is a long-lasting and well-known problem at European and international levels. Despite the existing legal frameworks and incentives, children remain deprived of many kinds of therapy because of challenges faced in appropriately study and tailoring medicinal and other products for them. In this context, the necessity to foster paediatric research addressing unsolved and uncovered issues within a ‘translational approach’ has appeared. This article, after having clarified the concept of translational research in the perspective of the establishment of a European paediatric research infrastructure (RI), will identify and point out ethical, legal and regulatory issues particularly relevant in a children’s rights perspective. It concludes asking for the setting up of an adequate model of governance within a future RI, including adequate and independent ethical oversight and a pluridisciplinary common service dealing with ethical, legal and societal issues relevant for children.

Genetic dysfunction of serotonin 2A receptor hampers response to antidepressant drugs: A translational approach

2016 ◽  
Vol 105 ◽  
pp. 142-153 ◽  
Author(s):  
Gaël Qesseveur ◽  
Anne Cécile Petit ◽  
Hai Thanh Nguyen ◽  
Lionel Dahan ◽  
Romain Colle ◽  
...  
Keyword(s):  
Antidepressant Drugs ◽  
Serotonin 2A Receptor ◽  
Translational Approach ◽  
Serotonin 2A

Translational approach to study flexibility as an endophenotype of obsessive compulsive disorders

2014 ◽  
Vol 29 (S3) ◽  
pp. 546-546
Author(s):  
N. Benzina ◽  
S.L. Mondragon ◽  
N. Ouarti ◽  
L. Mallet ◽  
E. Burguiere
Keyword(s):  
Reversal Learning ◽  
Behavioral Flexibility ◽  
Repetitive Behaviors ◽  
Reward Contingency ◽  
Neural Basis ◽  
Obsessive Compulsive ◽  
Compulsive Behaviors ◽  
Translational Approach ◽  
Obsessive Compulsive Disorders ◽  
Compulsive Disorders

Behavioral flexibility is the ability of a subject to change its behavior according to contextual cues. In humans, Obsessive Compulsive Disorders (OCD) is characterized by repetitive behavior, performed through rigid rituals. This phenomenological observation has led to explore the idea that OCD patients may have diminished behavioral flexibility. To address this question we developed innovative translational approaches across multiple species, including human patients suffering from obsessive-compulsive disorders, and rodent genetic models of OCD to provide original data in the perspective of enlightening the neurocognitive bases of compulsive behaviors. Behavioral flexibility may be challenged in experimental tasks such as reversal learning paradigms. In these tasks, the subject has to respond to either of two different visual stimuli but only one stimulus is positively rewarded while the other is not. After this first association has been learned, reward contingency are inverted, so that the previously neutral stimulus is now rewarded, while the previously rewarded stimulus is not. Performance in reversal learning is indexed by the number of perseverative errors committed when participants maintain their response towards previously reinforced stimulus in spite of negative reward. Unsurprisingly, this behavioral task has been adapted to mice using various response modalities (T-maze, lever press, nose-poke). Using animal models of compulsive behaviors give much more possibilities to study the deficient functions and their underlying neural basis that could lead to pathological repetitive behaviors. Here we present new behavioral set-ups that we developed in parallel in human (i.e. healthy subjects and OCD patients) and mice (i.e. controls and SAPAP3-KO mice) to study the role of the behavioral flexibility as a possible endophenotype of OCD. We observed that the subjects suffering of compulsive behaviors showed perseverative maladaptive behaviors in these tasks. By comparing the results of a similar task-design in humans and mouse models we will discuss the pertinence of such translational approach to further study the neurocognitive basis of compulsive behaviors.

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