Edible additive effects on zebrafish cardiovascular functionality with hydrodynamic assessment

Abstract Food coloring is often used as a coloring agent in foods, medicines and cosmetics, and it was reported to have certain carcinogenic and mutagenic effects in living organisms. Investigation of physiological parameters using zebrafish is a promising methodology to understand disease biology and drug toxicity for various drug discovery on humans. Zebrafish (Danio rerio) is a well-acknowledged model organism with combining assets such as body transparency, small size, low cost of cultivation, and high genetic homology with humans and is used as a specimen tool for the in-vivo throughput screening approach. In addition, recent advances in microfluidics show a promising alternative for zebrafish manipulation in terms of drug administration and extensive imaging capability. This pilot work highlighted the design and development of a microfluidic detection platform for zebrafish larvae through investigating the effects of food coloring on cardiovascular functionality and pectoral fin swing ability. The zebrafish embryos were exposed to the Cochineal Red and Brilliant Blue FCF pigment solution in a concentration of (0.02‰, 0.2‰) cultured in the laboratory from the embryo stage to hatching and development until 9 days post fertilization (d.p.f.). In addition, zebrafish swimming behaviors in terms of pectoral fin beating towards the toxicity screening were further studied by visualizing the induced flow field. It was evidenced that Cochineal Red pigment at a concentration of 0.2‰ not only significantly affected the zebrafish pectoral fin swing behavior, but also significantly increased the heart rate of juvenile fish. The higher concentration of Brilliant Blue FCF pigment (0.2%) increased heart rate during early embryonic stages of zebrafish. However, zebrafish exposed to food coloring did not show any significant changes in cardiac output. The applications of this proposed platform can be further extended towards observing the neurobiological/hydrodynamic behaviors of zebrafish larvae for practical applications in drug tests.

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In vivo Modelling of Toxicity of Eight Commercial Artificial Sweeteners in Daphnia Neonates and Zebrafish Embryos through Cardiac Performance Assessments

10.20944/preprints202009.0419.v1 ◽

2020 ◽

Author(s):

Ferry Saputra ◽

Yu-Heng Lai ◽

Rey Arturo Fernandez ◽

Allan Patrick G. Macabeo ◽

Hong-Thih Lai ◽

...

Keyword(s):

Heart Rate ◽

Adverse Effects ◽

Cardiac Performance ◽

Calorie Intake ◽

Artificial Sweeteners ◽

Artificial Sweetener ◽

Food Ingredients ◽

Zebrafish Larvae ◽

Sodium Cyclamate

Artificial sweeteners are widely used food ingredients in beverages and drinks to lower calorie intake which in turn prevent lifestyle diseases such as obesity. Epidemiological evidences suggest that an overdose of artificial sweeteners could result to adverse effects after consumption. Thus, our study aims to systematically explore the potential adverse effects of eight commercial artificial sweeteners, including acesulfame-K, alitame, aspartame, sodium cyclamate, dulcin, neotame, saccharin and sucralose on cardiac performances of zebrafish (Danio rerio) and Daphnia as model animals. Embryonic zebrafish and Daphnia were exposed to eight artificial sweeteners at 100 ppb concentrations and their cardiac performance (heart rate, ejection fraction, fractional shortening, stroke volume, cardiac output and heartbeat regularity) were measured and compared. Saccharin significantly increased the heart rate of zebrafish larvae while a significant decrease was observed in Daphnia. Significant increase was also noted in zebrafish heart rate variability after incubation in acesulfame K, dulcin, sodium cyclamate, and sucralose. However, a significant increase in Daphnia was only observed after incubation in dulcin. Based on Principal Component Analysis (PCA) and hierarchical clustering results, several artificial sweetener samples were species-specific to zebrafish and Daphnia. Our study demonstrates the potential adverse physiological effects of artificial sweeteners in cardiovascular systems of zebrafish larvae and Daphnia.

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Baicalin Represses Type Three Secretion System of Pseudomonas aeruginosa through PQS System

Molecules ◽

10.3390/molecules26061497 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1497

Author(s):

Pansong Zhang ◽

Qiao Guo ◽

Zhihua Wei ◽

Qin Yang ◽

Zisheng Guo ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Virulence Factors ◽

Mammalian Cells ◽

Secretion System ◽

Chinese Herbs ◽

Infection Model ◽

Lung Pathology ◽

Promising Alternative ◽

The Impact

Therapeutics that target the virulence of pathogens rather than their viability offer a promising alternative for treating infectious diseases and circumventing antibiotic resistance. In this study, we searched for anti-virulence compounds against Pseudomonas aeruginosa from Chinese herbs and investigated baicalin from Scutellariae radix as such an active anti-virulence compound. The effect of baicalin on a range of important virulence factors in P. aeruginosa was assessed using luxCDABE-based reporters and by phenotypical assays. The molecular mechanism of the virulence inhibition by baicalin was investigated using genetic approaches. The impact of baicalin on P. aeruginosa pathogenicity was evaluated by both in vitro assays and in vivo animal models. The results show that baicalin diminished a plenty of important virulence factors in P. aeruginosa, including the Type III secretion system (T3SS). Baicalin treatment reduced the cellular toxicity of P. aeruginosa on the mammalian cells and attenuated in vivo pathogenicity in a Drosophila melanogaster infection model. In a rat pulmonary infection model, baicalin significantly reduced the severity of lung pathology and accelerated lung bacterial clearance. The PqsR of the Pseudomonas quinolone signal (PQS) system was found to be required for baicalin’s impact on T3SS. These findings indicate that baicalin is a promising therapeutic candidate for treating P. aeruginosa infections.

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Histological, Biomechanical, and Biological Properties of Genipin-Crosslinked Decellularized Peripheral Nerves

International Journal of Molecular Sciences ◽

10.3390/ijms22020674 ◽

2021 ◽

Vol 22 (2) ◽

pp. 674

Author(s):

Óscar Darío García-García ◽

Marwa El Soury ◽

David González-Quevedo ◽

David Sánchez-Porras ◽

Jesús Chato-Astrain ◽

...

Keyword(s):

Ex Vivo ◽

Nerve Repair ◽

Wistar Rat ◽

Biomechanical Properties ◽

Biological Properties ◽

Suitable Alternative ◽

Promising Alternative ◽

Histological Pattern ◽

The Impact

Acellular nerve allografts (ANGs) represent a promising alternative in nerve repair. Our aim is to improve the structural and biomechanical properties of biocompatible Sondell (SD) and Roosens (RS) based ANGs using genipin (GP) as a crosslinker agent ex vivo. The impact of two concentrations of GP (0.10% and 0.25%) on Wistar rat sciatic nerve-derived ANGs was assessed at the histological, biomechanical, and biocompatibility levels. Histology confirmed the differences between SD and RS procedures, but not remarkable changes were induced by GP, which helped to preserve the nerve histological pattern. Tensile test revealed that GP enhanced the biomechanical properties of SD and RS ANGs, being the crosslinked RS ANGs more comparable to the native nerves used as control. The evaluation of the ANGs biocompatibility conducted with adipose-derived mesenchymal stem cells cultured within the ANGs confirmed a high degree of biocompatibility in all ANGs, especially in RS and RS-GP 0.10% ANGs. Finally, this study demonstrates that the use of GP could be an efficient alternative to improve the biomechanical properties of ANGs with a slight impact on the biocompatibility and histological pattern. For these reasons, we hypothesize that our novel crosslinked ANGs could be a suitable alternative for future in vivo preclinical studies.

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Heterodimer Formation of the Homodimeric ABC Transporter OpuA

International Journal of Molecular Sciences ◽

10.3390/ijms22115912 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5912

Author(s):

Patricia Alvarez-Sieiro ◽

Hendrik R. Sikkema ◽

Bert Poolman

Keyword(s):

Abc Transporter ◽

Conformational Dynamics ◽

Host Organism ◽

Affinity Tag ◽

Practical Applications ◽

Fundamental Research ◽

Protein Multimerization ◽

Biochemical Analyses

Many proteins have a multimeric structure and are composed of two or more identical subunits. While this can be advantageous for the host organism, it can be a challenge when targeting specific residues in biochemical analyses. In vitro splitting and re-dimerization to circumvent this problem is a tedious process that requires stable proteins. We present an in vivo approach to transform homodimeric proteins into apparent heterodimers, which then can be purified using two-step affinity-tag purification. This opens the door to both practical applications such as smFRET to probe the conformational dynamics of homooligomeric proteins and fundamental research into the mechanism of protein multimerization, which is largely unexplored for membrane proteins. We show that expression conditions are key for the formation of heterodimers and that the order of the differential purification and reconstitution of the protein into nanodiscs is important for a functional ABC-transporter complex.

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Automatic and Robust Estimation of Heart Rate in Zebrafish Larvae

IEEE Transactions on Automation Science and Engineering ◽

10.1109/tase.2017.2705240 ◽

2018 ◽

Vol 15 (3) ◽

pp. 1041-1052 ◽

Cited By ~ 2

Author(s):

Syam Krishna ◽

Kiranam Chatti ◽

Ramesh R. Galigekere

Keyword(s):

Heart Rate ◽

Robust Estimation ◽

Zebrafish Larvae

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Fucoidan But Not 2′-Fucosyllactose Inhibits Human Norovirus Replication in Zebrafish Larvae

Viruses ◽

10.3390/v13030461 ◽

2021 ◽

Vol 13 (3) ◽

pp. 461

Author(s):

Malcolm Turk Hsern Tan ◽

Yan Li ◽

Mohamad Eshaghi Gorji ◽

Zhiyuan Gong ◽

Dan Li

Keyword(s):

Brown Algae ◽

Disease Burden ◽

Type A ◽

Fucus Vesiculosus ◽

Human Norovirus ◽

Human Noroviruses ◽

Molecular Weights ◽

Zebrafish Larvae ◽

Virus Like Particle

Human noroviruses (hNoVs) cause heavy disease burden worldwide and there is no clinically approved vaccination or antiviral hitherto. In this study, with the use of a zebrafish larva in vivo platform, we investigated the anti-hNoV potentials of fucoidan (from brown algae Fucus vesiculosus) and 2′-Fucosyllactose (2′-FL). As a result, although both fucoidan and 2′-FL were able to block hNoV GII.4 virus-like particle (VLPs) from binding to type A saliva as expected, only fucoidan, but not 2′-FL, was able to inhibit the replication of hNoV GII.P16-GII.4 in zebrafish larvae, indicating the possible needs of higher molecular weights for fucosylated carbohydrates to exert anti-hNoV effect.

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In vivo optical endomicroscopy: two decades of translational research towards next generation diagnosis of eosinophilic esophagitis

Translational Medicine Communications ◽

10.1186/s41231-020-00080-z ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Andreas Wartak ◽

John G. Garber ◽

Qian Yuan ◽

Wayne G. Shreffler ◽

Paul E. Hesterberg ◽

...

Keyword(s):

Eosinophilic Esophagitis ◽

Massachusetts General Hospital ◽

Standard Of Care ◽

Depth Information ◽

Current Standard ◽

Promising Alternative ◽

White Light Endoscopy ◽

Related Risk ◽

Histopathologic Analysis

AbstractHistopathologic analysis of biopsy specimens obtained via white light endoscopy (WLE) is the gold standard for the diagnosis of several mucosal diseases in the upper gastrointestinal (GI) tract. However, this standard of care entails a series of critical shortcomings such as missing depth information, high costs, time inefficiency, low-resolution imaging in vivo, high sampling variability, missing intrinsic tissue-specific contrast, and anesthesia related risk. In the quest for a diagnostic technology to replace the current standard of care, in vivo optical endomicroscopy has emerged as a promising alternative. This paper tells the story of a cluster of optical microscopy-based modalities invented, further developed, or first-validated in the laboratory of Dr. Guillermo J. Tearney (Tearney Lab) at the Wellman Center for Photomedicine of Massachusetts General Hospital over the past two decades, that combined lead to a novel method for diagnosis of eosinophilic esophagitis (EoE). Rather than being a comprehensive literature review, this paper aims to describe the translational journey towards a disease specific diagnostic and research tool for this increasingly recognized yet poorly understood immune-mediated disorder of the esophagus.

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Heart rate reduction with ivabradine promotes shear stress-dependent anti-inflammatory mechanisms in arteries

Thrombosis and Haemostasis ◽

10.1160/th16-03-0214 ◽

2016 ◽

Vol 116 (07) ◽

pp. 181-190 ◽

Cited By ~ 13

Author(s):

Luong Le ◽

Hayley Duckles ◽

Torsten Schenkel ◽

Marwa Mahmoud ◽

Jordi Tremoleda ◽

...

Keyword(s):

Heart Rate ◽

Shear Stress ◽

Carotid Arteries ◽

Vascular Inflammation ◽

Protective Effects ◽

En Face ◽

Inflammatory Activation ◽

Anti Inflammatory ◽

Stress Dependent

SummaryBlood flow generates wall shear stress (WSS) which alters endothelial cell (EC) function. Low WSS promotes vascular inflammation and atherosclerosis whereas high uniform WSS is protective. Ivabradine decreases heart rate leading to altered haemodynamics. Besides its cardio-protective effects, ivabradine protects arteries from inflammation and atherosclerosis via unknown mechanisms. We hypothesised that ivabradine protects arteries by increasing WSS to reduce vascular inflammation. Hypercholesterolaemic mice were treated with ivabradine for seven weeks in drinking water or remained untreated as a control. En face immunostaining demonstrated that treatment with ivabradine reduced the expression of pro-inflammatory VCAM-1 (p<0.01) and enhanced the expression of anti-inflammatory eNOS (p<0.01) at the inner curvature of the aorta. We concluded that ivabradine alters EC physiology indirectly via modulation of flow because treatment with ivabradine had no effect in ligated carotid arteries in vivo, and did not influence the basal or TNFα-induced expression of inflammatory (VCAM-1, MCP-1) or protective (eNOS, HMOX1, KLF2, KLF4) genes in cultured EC. We therefore considered whether ivabradine can alter WSS which is a regulator of EC inflammatory activation. Computational fluid dynamics demonstrated that ivabradine treatment reduced heart rate by 20 % and enhanced WSS in the aorta. In conclusion, ivabradine treatment altered haemodynamics in the murine aorta by increasing the magnitude of shear stress. This was accompanied by induction of eNOS and suppression of VCAM-1, whereas ivabradine did not alter EC that could not respond to flow. Thus ivabradine protects arteries by altering local mechanical conditions to trigger an anti-inflammatory response.

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Cardiovascular Responding during Anger and Fear Imagery

Psychological Reports ◽

10.2466/pr0.1982.50.1.219 ◽

1982 ◽

Vol 50 (1) ◽

pp. 219-230 ◽

Cited By ~ 53

Author(s):

Richard J. Roberts ◽

Theodore C. Weerts

Keyword(s):

College Students ◽

Blood Pressure ◽

Heart Rate ◽

Systolic Blood Pressure ◽

Diastolic Blood Pressure ◽

Scene Change ◽

Emotional Responding ◽

Analysis Of Change ◽

Screening Interview

This study was designed to determine if visualization of anger- and fear-provoking scenes produced differential physiological patterns similar to those produced by in vivo manipulations. Normotensive college students were selected on the basis of their responses to newly developed Anger and Fear/Anxiety questionnaires and for their ability to construct arousing scenes during a screening interview. In a 2 × 2 design (intensity × emotion), four scenes (high and low anger, high and low fear) were constructed individually for each of 16 subjects to imagine. Diastolic blood pressure, systolic blood pressure, and heart rate were monitored during visualization of each scene. Change in diastolic blood pressure was significantly greater for high anger than for high fear as predicted. Analysis of change in heart rate and systolic blood pressure showed significant effects for intensity only. These results provide further support for the concept of physiological differentiation in human emotion and suggest the utility of imagery for systematic study of human emotional responding.

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