Effects of sleep modulation during pregnancy in the mother and offspring: Evidences from preclinical research

2020 ◽  
Author(s):  
Gabriel Natan Pires ◽  
Luciana Benedetto ◽  
Rene Cortese ◽  
David Gozal ◽  
Kamalesh K. Gulia ◽  
...  
Keyword(s):  
Preclinical Research ◽  
Sleep Modulation

[18F]-florbetaben PET/CT Imaging in the Alzheimer’s Disease Mouse Model APPswe/PS1dE9

2018 ◽  
Vol 16 (1) ◽  
pp. 49-55 ◽  
Author(s):  
J. Stenzel ◽  
C. Rühlmann ◽  
T. Lindner ◽  
S. Polei ◽  
S. Teipel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
New Drugs ◽  
Imaging Data ◽  
Wild Type ◽  
Preclinical Research ◽  
Standardized Uptake Values ◽  
Pet Ct

Background: Positron-emission-tomography (PET) using 18F labeled florbetaben allows noninvasive in vivo-assessment of amyloid-beta (Aβ), a pathological hallmark of Alzheimer’s disease (AD). In preclinical research, [<sup>18</sup>F]-florbetaben-PET has already been used to test the amyloid-lowering potential of new drugs, both in humans and in transgenic models of cerebral amyloidosis. The aim of this study was to characterize the spatial pattern of cerebral uptake of [<sup>18</sup>F]-florbetaben in the APPswe/ PS1dE9 mouse model of AD in comparison to histologically determined number and size of cerebral Aβ plaques. Methods: Both, APPswe/PS1dE9 and wild type mice at an age of 12 months were investigated by smallanimal PET/CT after intravenous injection of [<sup>18</sup>F]-florbetaben. High-resolution magnetic resonance imaging data were used for quantification of the PET data by volume of interest analysis. The standardized uptake values (SUVs) of [<sup>18</sup>F]-florbetaben in vivo as well as post mortem cerebral Aβ plaque load in cortex, hippocampus and cerebellum were analyzed. Results: Visual inspection and SUVs revealed an increased cerebral uptake of [<sup>18</sup>F]-florbetaben in APPswe/ PS1dE9 mice compared with wild type mice especially in the cortex, the hippocampus and the cerebellum. However, SUV ratios (SUVRs) relative to cerebellum revealed only significant differences in the hippocampus between the APPswe/PS1dE9 and wild type mice but not in cortex; this differential effect may reflect the lower plaque area in the cortex than in the hippocampus as found in the histological analysis. Conclusion: The findings suggest that histopathological characteristics of Aβ plaque size and spatial distribution can be depicted in vivo using [<sup>18</sup>F]-florbetaben in the APPswe/PS1dE9 mouse model.

SGLT-2 Inhibition: Novel Therapeutics for Reno-and Cardioprotection in Diabetes Mellitus

2019 ◽  
Vol 15 (5) ◽  
pp. 349-356 ◽  
Author(s):  
Angus Gill ◽  
Stephen P. Gray ◽  
Karin A. Jandeleit-Dahm ◽  
Anna M.D. Watson
Keyword(s):  
Sympathetic Nerve Activity ◽  
Diabetic Patients ◽  
Protective Effects ◽  
Preclinical Research ◽  
Type 2 Diabetic Patients ◽  
Nerve Activity ◽  
Current State ◽  
Glucose Reabsorption ◽  
Type 2 Diabetic

Background: The sodium glucose co-transporter 2 (SGLT2) is primarily located within S1 of the renal proximal tubule being responsible for approximately 90% of glucose re-uptake in the kidney. Inhibition of SGLT2 is an exciting new pharmacological approach for the reduction of blood glucose in type 2 diabetic patients via inhibition of tubular glucose reabsorption. In addition to lowering glucose, this group of drugs has shown significant cardiovascular and renal protective effects. Conclusion: This review aims to outline the current state of preclinical research and clinical trials for different SGLT2 inhibitors and outline some of the proposed mechanisms of action, including possible effects on sympathetic nerve activity, which may contribute to the unexpected beneficial cardiovascular and reno-protective effects of this class of compounds.

scholarly journals Cannabidiol Modulates the Motivational and Anxiety-Like Effects of 3,4-Methylenedioxypyrovalerone (MDPV) in Mice

2021 ◽  
Vol 22 (15) ◽  
pp. 8304
Author(s):  
Laia Alegre-Zurano ◽  
Raúl López-Arnau ◽  
Miguel Á. Luján ◽  
Jordi Camarasa ◽  
Olga Valverde
Keyword(s):  
Conditioned Place Preference ◽  
Learning Task ◽  
Place Preference ◽  
Bath Salts ◽  
Self Administration ◽  
Preclinical Research ◽  
Plus Maze ◽  
Life Threatening ◽  
Synthetic Cathinone ◽  
High Responders

3,4-Methylenedioxypyrovalerone (MDPV) is a new psychoactive substance (NPS) and the most widespread and life-threatening synthetic cathinone of the “bath salts”. Preclinical research has proven the cocaine-like psychostimulant effects of MDPV and its potential for abuse. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid that has emerged as a new potential treatment for drug addiction. Here, we tested the effects of CBD (20 mg/kg) on MDPV (2 mg/kg)-induced conditioned place preference and MDPV (0.05 and 0.075 mg/kg/infusion) self-administration paradigms. In addition, we assessed the effects of the co-administration of CBD and MDPV (3 and 4 mg/kg) on anxiety-like behaviour using the elevated plus maze (EPM). CBD mitigated the MDPV-induced conditioned place preference. On the contrary, CBD administration throughout the MDPV (0.075 mg/kg/infusion) self-administration increased drug-seeking and taking behaviours, but only in the high-responders group of mice. Furthermore, CBD exerted anxiolytic-like effects, exclusively in MDPV-treated mice. Taken together, our results indicate that CBD modulation of MDPV-induced motivational responses in mice varies depending on the requirements of the learning task, resulting in a complex response. Therefore, further research attempting to decipher the behavioural and molecular interactions between CBD and MDPV is needed.

scholarly journals Are We Paving the Way to Dig Out of the “Pandemic Hole”? A Narrative Review on SARS-CoV-2 Vaccination: From Animal Models to Human Immunization

2021 ◽  
Vol 9 (3) ◽  
pp. 53
Author(s):  
Giuseppe Tardiolo ◽  
Pina Brianti ◽  
Daniela Sapienza ◽  
Pia dell’Utri ◽  
Viviane Di Dio ◽  
...  
Keyword(s):  
Animal Models ◽  
Viral Vector ◽  
Herd Immunity ◽  
Population Level ◽  
Narrative Review ◽  
Therapeutic Interventions ◽  
Preclinical Research ◽  
Inactivated Vaccines ◽  
Preclinical And Clinical Studies ◽  
Social Upheaval

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new pathogen agent causing the coronavirus infectious disease (COVID-19). This novel virus originated the most challenging pandemic in this century, causing economic and social upheaval internationally. The extreme infectiousness and high mortality rates incentivized the development of vaccines to control this pandemic to prevent further morbidity and mortality. This international scenario led academic scientists, industries, and governments to work and collaborate strongly to make a portfolio of vaccines available at an unprecedented pace. Indeed, the robust collaboration between public systems and private companies led to resolutive actions for accelerating therapeutic interventions and vaccines mechanism. These strategies contributed to rapidly identifying safe and effective vaccines as quickly and efficiently as possible. Preclinical research employed animal models to develop vaccines that induce protective and long-lived immune responses. A spectrum of vaccines is worldwide under investigation in various preclinical and clinical studies to develop both individual protection and safe development of population-level herd immunity. Companies employed and developed different technological approaches for vaccines production, including inactivated vaccines, live-attenuated, non-replicating viral vector vaccines, as well as acid nucleic-based vaccines. In this view, the present narrative review provides an overview of current vaccination strategies, taking into account both preclinical studies and clinical trials in humans. Furthermore, to better understand immunization, animal models on SARS-CoV-2 pathogenesis are also briefly discussed.

scholarly journals Cannabidiol as a Potential Treatment for Anxiety and Mood Disorders: Molecular Targets and Epigenetic Insights from Preclinical Research

2021 ◽  
Vol 22 (4) ◽  
pp. 1863
Author(s):  
Philippe A. Melas ◽  
Maria Scherma ◽  
Walter Fratta ◽  
Carlo Cifani ◽  
Paola Fadda
Keyword(s):  
Mood Disorders ◽  
Cannabinoid Receptors ◽  
Transient Receptor Potential ◽  
Therapeutic Potential ◽  
Molecular Targets ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Preclinical Research ◽  
Neuropsychiatric Diseases ◽  
Transient Receptor

Cannabidiol (CBD) is the most abundant non-psychoactive component of cannabis; it displays a very low affinity for cannabinoid receptors, facilitates endocannabinoid signaling by inhibiting the hydrolysis of anandamide, and stimulates both transient receptor potential vanilloid 1 and 2 and serotonin type 1A receptors. Since CBD interacts with a wide variety of molecular targets in the brain, its therapeutic potential has been investigated in a number of neuropsychiatric diseases, including anxiety and mood disorders. Specifically, CBD has received growing attention due to its anxiolytic and antidepressant properties. As a consequence, and given its safety profile, CBD is considered a promising new agent in the treatment of anxiety and mood disorders. However, the exact molecular mechanism of action of CBD still remains unknown. In the present preclinical review, we provide a summary of animal-based studies that support the use of CBD as an anxiolytic- and antidepressant-like compound. Next, we describe neuropharmacological evidence that links the molecular pharmacology of CBD to its behavioral effects. Finally, by taking into consideration the effects of CBD on DNA methylation, histone modifications, and microRNAs, we elaborate on the putative role of epigenetic mechanisms in mediating CBD’s therapeutic outcomes.

The functional vascular anatomy of the swine for research

Vascular ◽  
2021 ◽  
pp. 170853812199650
Author(s):  
Joseph Edwards ◽  
Hossam Abdou ◽  
Neerav Patel ◽  
Marta J Madurska ◽  
Kelly Poe ◽  
...  
Keyword(s):  
Translational Research ◽  
Functional Anatomy ◽  
Three Dimensional ◽  
Vascular Anatomy ◽  
Review Article ◽  
Imaging Data ◽  
Preclinical Research ◽  
Iodinated Contrast ◽  
Translational Research Program ◽  
And Function

Objectives Swine ( Sus Scrofa) are utilized broadly in research settings, given similarities to human vessel size and function; however, there are some important differences for clinicians to understand in order to interpret and perform translational research. This review article uses angiograms acquired in the course of a translational research program to present a description of the functional anatomy of the swine. Methods Digital subtraction angiography and computed tomography angiography were obtained throughout the course of multiple studies utilizing power injection with iodinated contrast. Subtracted two-dimensional images and three-dimensional multiplanar reformations were utilized post image acquisition to create maximal intensity projections and three-dimensional renderings of using open-source software (OsiriX). These imaging data are presented along with vessel measurements for reference. Results An atlas highlighting swine vascular anatomy, with an emphasis on inter-species differences that may influence how studies are conducted and interpreted, was compiled. Conclusions Swine are utilized in broad-reaching fields for preclinical research. While many similarities between human and swine vasculature exist, there are important differences to consider when conducting and interpreting research. This review article highlights these differences and presents accompanying images to inform clinicians gaining experience in swine research.

scholarly journals The National Institute of Mental Health: Research Agenda and Priorities in Geriatrics and Aging

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 621-621
Author(s):  
Elizabeth Necka
Keyword(s):  
Mental Health ◽  
Social Isolation ◽  
Suicide Prevention ◽  
Research Agenda ◽  
Behavioral Science ◽  
Late Life ◽  
Mental Health Research ◽  
Preclinical Research ◽  
Affective Science ◽  
Prevention Interventions

Abstract The Geriatrics and Aging Processes Research Branch of the National Institute of Mental Health (NIMH) supports research on the etiology, pathophysiology, and trajectory of late life mental disorders. The branch encourages research using neuroscience, cognitive and affective science, and social and behavioral science to translate basic and preclinical research to clinical research. The branch prioritizes research that investigates neuropsychiatric disorders of aging, how they interact with neurodevelopment/neurodegeneration, and how to assess, treat, and prevent them. Of particular interest is research on social isolation and suicide. Suicide prevention research is an urgent priority: NIMH’s portfolio includes projects aimed at identifying those at risk for suicide, understanding causes of suicide risk, developing suicide prevention interventions, and testing the effectiveness of these interventions and services in real-world settings. In this talk, a NIMH program official will discuss the NIMH research agenda in the domain of late-life mental illness, social isolation, and suicide.

scholarly journals OP0248 DEVELOPMENT OF A 3D SKIN MICROTISSUE MODEL FOR FIBROTIC DISEASES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 151.2-152
Author(s):  
E. Pachera ◽  
G. Kania ◽  
A. Juengel ◽  
M. Calcagni ◽  
O. Distler
Keyword(s):  
Gene Expression ◽  
Noncoding Rna ◽  
Clinical Investigation ◽  
3D Culture ◽  
Human Keratinocytes ◽  
Dermal Fibroblasts ◽  
Proof Of Concept ◽  
Research Support ◽  
Preclinical Research ◽  
Matrix Gene

Background:Traditional preclinical approaches, such as two-dimensional cell culture and animal models, are often inadequate to mimic the pathophysiological features of complex diseases such as systemic sclerosis (SSc). Human specific targets, such as the recently described pro-fibrotic long non coding RNA (lncRNA) H19X1, are becoming increasingly relevant in preclinical research, creating the need of new strategies and tools in translational medicine. The employment of novel three-dimensional (3D) culture systems, where multiple cell types are included, is filling an important gap left by the traditional preclinical methods.Objectives:To develop an easy to produce 3D fibrotic skin microtissues model for translational proof of concept studies.Methods:Two thousand five hundred dermal fibroblasts isolated from skin of SSc patients were seeded in ultra-low attachment 96-well plates. Fibroblast were let to aggregate into spheres for 48h. Two thousand five hundred primary normal human keratinocytes were added to the culture and let to layer onto the fibroblast spheres for 72h. H19X silencing experiments were used as proof of concept studies. H19X silencing with antisense oligonucleotides or transfections with a scrambled control were performed in fibroblasts prior to the sphere formation for 24h. TGFβ (10 ng/ml) was added to microtissue to exacerbate the fibrotic phenotype. Haematoxylin eosin staining as well as immunohistochemistry staining for vimentin and cytokeratin 10 was performed. Skin microtissues were processed for RNA and protein isolation. Pro-collagen Iα1 and fibronectin were quantified in the supernatants with ELISA.Results:The microtissues presented a core of SSc fibroblast as revealed by vimentin staining and an external layer of keratinocytes as revealed by cytokeratin 10 staining, mimicking the human skin architecture. Gene expression analysis following TGFβ stimulation displayed induced expression of extracellular matrix gene COL1A1 (p=0.044) and the myofibroblast marker ACTA2 (p=0.018), indicating that the microtissues were able to develop a fibrotic response. Microtissues, where H19X was silenced, displayed reduced gene expression of COL1A1 and ACTA2 after TGFβ stimulation (COL1A1 p=0.007, ACTA2 p=0.045). Additionally, H19X silencing led to lower levels of αSMA protein expression (p=0.009) and pro-collagen1α1 secretion (p=0.039) in the supernatant of the microtissue cultures as revealed by Western Blot and ELISA, respectively. FN1 expression and fibronectin protein levels were not significantly reduced in the microtissues after H19X silencing.Conclusion:We were able to produce a 3D microtissue resembling skin architecture that can respond to fibrotic stimuli. Knockdown experiments of pro-fibrotic lncRNA H19X confirmed the potential of the model as screening platform for novel pro-fibrotic effectors. A future aim will be to optimize the model for high-throughput automated screening platforms.References:[1]Pachera, E., et al. (2020). “Long noncoding RNA H19X is a key mediator of TGF-β–driven fibrosis.” The Journal of Clinical Investigation 130(9): 4888-4905.Disclosure of Interests:Elena Pachera: None declared, Gabriela Kania: None declared, Astrid Juengel: None declared, Maurizio Calcagni Speakers bureau: Arthrex, Consultant of: Medartis, Arthrex, SilkBiomaterials, Grant/research support from: Medartis, Oliver Distler Speakers bureau: Actelion, Bayer, Boehringer Ingelheim, Medscape, Novartis, Roche, Consultant of: Abbvie, Actelion, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, ChemomAb, Corpuspharma, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, -Kymera, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi, UCB, Grant/research support from: Abbvie, Actelion, Bayer, Boehringer Ingelheim, Kymera Therapeutics, Mitsubishi Tanabe

scholarly journals The Nephroprotective Properties of Extracellular Vesicles in Experimental Models of Chronic Kidney Disease: a Systematic Review

2021 ◽  
Author(s):  
Natalia Nowak ◽  
Masayuki Yamanouchi ◽  
Eiichiro Satake
Keyword(s):  
Systematic Review ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Interstitial Fibrosis ◽  
Cell Damage ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Extracellular Vesicle ◽  
Experimental Models ◽  
Preclinical Research

AbstractExtracellular vesicle (EV)-based therapy was hypothesized as a promising regenerative approach which has led to intensive research of EVs in various pathologies. In this study, we performed a comprehensive systematic review of the current experimental evidence regarding the protective properties of EVs in chronic kidney disease (CKD). We evaluated the EV-based experiments, EV characteristics, and effector molecules with their involvement in CKD pathways. Including all animal records with available creatinine or urea data, we performed a stratified univariable meta-analysis to assess the determinants of EV-based therapy effectiveness. We identified 35 interventional studies that assessed nephroprotective role of EVs and catalogued them according to their involvement in CKD mechanism. Systematic assessment of these studies suggested that EVs had consistently improved glomerulosclerosis, interstitial fibrosis, and cell damage, among different CKD models. Moreover, EV-based therapy reduced the progression of renal decline in CKD. The stratified analyses showed that the disease model, administered dose, and time of therapeutic intervention were potential predictors of therapeutic efficacy. Together, EV therapy is a promising approach for CKD progression in experimental studies. Further standardisation of EV-methods, continuous improvement of the study quality, and better understanding of the determinants of EV effectiveness will facilitate preclinical research, and may help development of clinical trials in people with CKD. Graphical Abstract

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