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Article ; Online: Editorial

Mark Gray / Stefano Guido / Abirami Kugadas

Frontiers in Veterinary Science, Vol

The use of large animal models to improve pre-clinical translational research

2022 Volume 9

Keywords	disease models (animal) ; comparative model ; large animal models ; translational ; genetically altered animals ; Veterinary medicine ; SF600-1100
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Annurca apple polyphenol extract promotes mesenchymal-to-epithelial transition and inhibits migration in triple-negative breast cancer cells through ROS/JNK signaling

Daniela Cristina Vuoso / Stefania D’Angelo / Rosalia Ferraro / Sergio Caserta / Stefano Guido / Marcella Cammarota / Marina Porcelli / Giovanna Cacciapuoti

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 17

Abstract: Abstract Aberrant activation of epithelial-to-mesenchymal transition has been shown to correlate with triple-negative breast cancer (TNBC) progression and metastasis. Thus, the induction of the reverse process might offer promising opportunities to ... ...

Abstract	Abstract Aberrant activation of epithelial-to-mesenchymal transition has been shown to correlate with triple-negative breast cancer (TNBC) progression and metastasis. Thus, the induction of the reverse process might offer promising opportunities to restrain TNBC metastatic spreading and related mortality. Recently, the Annurca apple polyphenol extract (APE) has been highlighted as a multi-faceted agent that selectively kills TNBC cells by ROS generation and sustained JNK activation. Here, by qualitatively and quantitatively monitoring the real-time movements of live cells we provided the first evidence that APE inhibited the migration of MDA-MB-231 and MDA-MB-468 TNBC cells and downregulated metalloproteinase-2 and metalloproteinase-9. In MDA-MB-231 cells APE decreased SMAD-2/3 and p-SMAD-2/3 levels, increased E-cadherin/N-cadherin protein ratio, induced the switch from N-cadherin to E-cadherin expression and greatly reduced vimentin levels. Confocal and scanning electron microscopy imaging of APE-treated MDA-MB-231 cells evidenced a significant cytoskeletal vimentin and filamentous actin reorganization and revealed considerable changes in cell morphology highlighting an evident transition from the mesenchymal to epithelial phenotype with decreased migratory features. Notably, all these events were reverted by N-acetyl-l-cysteine and JNK inhibitor SP600125 furnishing evidence that APE exerted its effects through the activation of ROS/JNK signaling. The overall data highlighted APE as a potential preventing agent for TNBC metastasis.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Antibiofilm Properties of Temporin-L on Pseudomonas fluorescens in Static and In-Flow Conditions

Angela Di Somma / Federica Recupido / Arianna Cirillo / Alessia Romano / Alessandra Romanelli / Sergio Caserta / Stefano Guido / Angela Duilio

International Journal of Molecular Sciences, Vol 21, Iss 8526, p

2020 Volume 8526

Abstract: Biofilms consist of a complex microbial community adhering to biotic or abiotic surfaces and enclosed within a protein/polysaccharide self-produced matrix. The formation of this structure represents the most important adaptive mechanism that leads to ... ...

Abstract	Biofilms consist of a complex microbial community adhering to biotic or abiotic surfaces and enclosed within a protein/polysaccharide self-produced matrix. The formation of this structure represents the most important adaptive mechanism that leads to antibacterial resistance, and therefore, closely connected to pathogenicity. Antimicrobial peptides (AMPs) could represent attractive candidates for the design of new antibiotics because of their specific characteristics. AMPs show a broad activity spectrum, a relative selectivity towards their targets (microbial membranes), the ability to act on both proliferative and quiescent cells, a rapid mechanism of action, and above all, a low propensity for developing resistance. This article investigates the effect at subMIC concentrations of Temporin-L (TL) on biofilm formation in Pseudomonas fluorescens ( P. fluorescens ) both in static and dynamic conditions, showing that TL displays antibiofilm properties. Biofilm formation in static conditions was analyzed by the Crystal Violet assay. Investigation of biofilms in dynamic conditions was performed in a commercial microfluidic device consisting of a microflow chamber to simulate real flow conditions in the human body. Biofilm morphology was examined using Confocal Laser Scanning Microscopy and quantified via image analysis. The investigation of TL effects on P. fluorescens showed that when subMIC concentrations of this peptide were added during bacterial growth, TL exerted antibiofilm activity, impairing biofilm formation both in static and dynamic conditions. Moreover, TL also affects mature biofilm as confocal microscopy analyses showed that a large portion of preformed biofilm architecture was clearly perturbed by the peptide addition with a significative decrease of all the biofilm surface properties and the overall biomass. Finally, in these conditions, TL did not affect bacterial cells as the live/dead cell ratio remained unchanged without any increase in damaged cells, confirming an actual antibiofilm activity of ...
Keywords	biofilm ; antimicrobial peptide ; biofilm formation inhibition ; dynamic and static condition ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	540
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Transport efficiency in transdermal drug delivery: What is the role of fluid microstructure?

Liuzzi, Roberta / Antonio Carciati / Sergio Caserta / Stefano Guido

Colloids and surfaces. 2016 Mar. 01, v. 139

2016

Abstract: Interaction of microstructured fluids with skin is ubiquitous in everyday life, from the use of cosmetics, lotions, and drugs, to personal care with detergents or soaps. The formulation of microstructured fluids is crucial for the control of the ... ...

Abstract	Interaction of microstructured fluids with skin is ubiquitous in everyday life, from the use of cosmetics, lotions, and drugs, to personal care with detergents or soaps. The formulation of microstructured fluids is crucial for the control of the transdermal transport. In biomedical applications transdermal delivery is an efficient approach, alternative to traditional routes like oral and parenteral administration, for local release of drugs. Poor skin permeability, mainly due to its outer layer, which acts as the first barrier against the entry of external compounds, greatly limits the applicability of transdermal delivery. In this review, we focus on recent studies on the improvement of skin transport efficiency by using microemulsions (ME). Quantitative techniques, which are able to investigate both skin morphology and penetration processes, are also reviewed. ME are increasingly used as transdermal systems due to their low preparation cost, stability and high bioavailability. ME may act as penetration enhancers for many active principles, but ME microstructure should be chosen appropriately considering several factors such as ratio and type of ingredients and physic-chemical properties of the active components. ME microstructure is strongly affected by the flow conditions applied during processing, or during spreading and rubbing onto skin. Although the role played by ME microstructure has been generally recognized, the skin transport mechanisms associated with different ME microstructures are still to be elucidated and further investigations are required to fully exploit the potential of ME in transdermal delivery.
Keywords	bioavailability ; colloids ; cosmetics ; detergents ; drugs ; ingredients ; microstructure ; permeability ; quantitative analysis ; soaps
Language	English
Dates of publication	2016-0301
Size	p. 294-305.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	1500523-9
ISSN	1873-4367 ; 0927-7765
ISSN (online)	1873-4367
ISSN	0927-7765
DOI	10.1016/j.colsurfb.2015.11.064
Database	NAL-Catalogue (AGRICOLA)

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Article: Measuring Interfacial Tension of Emulsions in Situ by Microfluidics

D’Apolito, Rosa / Antonio Perazzo / Giovanna Tomaiuolo / Mariapia D’Antuono / Reinhard Miller / Stefano Guido / Valentina Preziosi

Langmuir. 2018 Apr. 11, v. 34, no. 17

2018

Abstract: Interfacial tension is a key parameter affecting industrially relevant properties of emulsions, such as morphology and stability. Although several methods are available to measure interfacial tension, they are based on generation of droplets starting ... ...

Abstract	Interfacial tension is a key parameter affecting industrially relevant properties of emulsions, such as morphology and stability. Although several methods are available to measure interfacial tension, they are based on generation of droplets starting from separate emulsion components and cannot directly probe the interfacial tension of an emulsion as such. Here, a novel microfluidic tensiometry device to measure interfacial tension of a water-in-oil emulsion in situ as a function of surfactant concentration is presented. In our approach, interfacial tension is obtained from a quantitative analysis of the deformation of individual emulsion droplets under steady state shear flow in microfluidic channels. The technique is validated by comparing the results with experimental data obtained by the pendant drop method in a broad range of interfacial tension values. A very good agreement is found, and an estimate of the surfactant critical micellar concentration (CMC) is also obtained. The proposed microfluidic setup can be used even at high surfactant concentrations, where the measurement is made more challenging by sample viscoelasticity, thus providing a powerful tool to determine the interfacial tension of complex systems in an extended concentration range. The technique could be also used for in-line monitoring of emulsion processing.
Keywords	deformation ; droplets ; emulsions ; monitoring ; quantitative analysis ; surface tension ; surfactants ; viscoelasticity
Language	English
Dates of publication	2018-0411
Size	p. 4991-4997.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	2005937-1
ISSN	1520-5827 ; 0743-7463
ISSN (online)	1520-5827
ISSN	0743-7463
DOI	10.1021/acs.langmuir.8b00208
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Modelling Neurological Diseases in Large Animals

Samantha L. Eaton / Fraser Murdoch / Nina M. Rzechorzek / Gerard Thompson / Claudia Hartley / Benjamin Thomas Blacklock / Chris Proudfoot / Simon G. Lillico / Peter Tennant / Adrian Ritchie / James Nixon / Paul M. Brennan / Stefano Guido / Nadia L. Mitchell / David N. Palmer / C. Bruce A. Whitelaw / Jonathan D. Cooper / Thomas M. Wishart

Cells, Vol 11, Iss 2641, p

Criteria for Model Selection and Clinical Assessment

2022 Volume 2641

Abstract: Issue: The impact of neurological disorders is recognised globally, with one in six people affected in their lifetime and few treatments to slow or halt disease progression. This is due in part to the increasing ageing population, and is confounded by ... ...

Abstract	Issue: The impact of neurological disorders is recognised globally, with one in six people affected in their lifetime and few treatments to slow or halt disease progression. This is due in part to the increasing ageing population, and is confounded by the high failure rate of translation from rodent-derived therapeutics to clinically effective human neurological interventions. Improved translation is demonstrated using higher order mammals with more complex/comparable neuroanatomy. These animals effectually span this translational disparity and increase confidence in factors including routes of administration/dosing and ability to scale, such that potential therapeutics will have successful outcomes when moving to patients. Coupled with advancements in genetic engineering to produce genetically tailored models, livestock are increasingly being used to bridge this translational gap. Approach: In order to aid in standardising characterisation of such models, we provide comprehensive neurological assessment protocols designed to inform on neuroanatomical dysfunction and/or lesion(s) for large animal species. We also describe the applicability of these exams in different large animals to help provide a better understanding of the practicalities of cross species neurological disease modelling. Recommendation: We would encourage the use of these assessments as a reference framework to help standardise neurological clinical scoring of large animal models.
Keywords	neurological disease ; large animal model ; clinical assessment ; model selection criteria ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Water evaporation from porous media by Dynamic Vapor Sorption

Donnarumma, Dario / Giovanna Tomaiuolo / Sergio Caserta / Stefano Guido / Yonas Gizaw

Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2015 Sept. 05, v. 480

2015

Abstract: Evaporation from porous media is a subject of growing interest in view of its industrial relevance and of the different spatial scales involved in the problem. A common, yet not fully elucidated feature of evaporation from porous media is the presence of ...

Abstract	Evaporation from porous media is a subject of growing interest in view of its industrial relevance and of the different spatial scales involved in the problem. A common, yet not fully elucidated feature of evaporation from porous media is the presence of a constant drying rate phase (CDP), which is followed by a falling drying rate phase (FDP). Here, we use a cotton fabric as a model porous medium and study the effects of salts and surfactants on CDP and FDP of aqueous solutions by using the Dynamic Vapor Sorption (DVS) technique. The cotton samples were first characterized by adsorption/desorption isotherms. Then the drying process of fabrics soaked in distilled water and in aqueous solutions at different hardness was investigated. The same procedure was used to study the drying of a dilute surfactant aqueous solution. All these experiments show that the presence of salts and surfactants in water affects the CDP, but not the FDP. At variance with the bulk behavior, an increase of the CDP drying rate was found for the surfactant solution and for aqueous salt solutions up to some hardness value.
Keywords	adsorption ; aqueous solutions ; cotton ; cotton fabric ; desorption ; drying ; evaporation ; hardness ; porous media ; salts ; surfactants ; vapors ; variance
Language	English
Dates of publication	2015-0905
Size	p. 159-164.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	1500517-3
ISSN	0927-7757
ISSN	0927-7757
DOI	10.1016/j.colsurfa.2014.11.011
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Cross-species efficacy of enzyme replacement therapy for CLN1 disease in mice and sheep

Hemanth R. Nelvagal / Samantha L. Eaton / Sophie H. Wang / Elizabeth M. Eultgen / Keigo Takahashi / Steven Q. Le / Rachel Nesbitt / Joshua T. Dearborn / Nicholas Siano / Ana C. Puhl / Patricia I. Dickson / Gerard Thompson / Fraser Murdoch / Paul M. Brennan / Mark Gray / Stephen N. Greenhalgh / Peter Tennant / Rachael Gregson / Eddie Clutton /

James Nixon / Chris Proudfoot / Stefano Guido / Simon G. Lillico / C. Bruce A. Whitelaw / Jui-Yun Lu / Sandra L. Hofmann / Sean Ekins / Mark S. Sands / Thomas M. Wishart / Jonathan D. Cooper

The Journal of Clinical Investigation, Vol 132, Iss

2022 Volume 20

Abstract: CLN1 disease, also called infantile neuronal ceroid lipofuscinosis (NCL) or infantile Batten disease, is a fatal neurodegenerative lysosomal storage disorder resulting from mutations in the CLN1 gene encoding the soluble lysosomal enzyme palmitoyl- ... ...

Abstract	CLN1 disease, also called infantile neuronal ceroid lipofuscinosis (NCL) or infantile Batten disease, is a fatal neurodegenerative lysosomal storage disorder resulting from mutations in the CLN1 gene encoding the soluble lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1). Therapies for CLN1 disease have proven challenging because of the aggressive disease course and the need to treat widespread areas of the brain and spinal cord. Indeed, gene therapy has proven less effective for CLN1 disease than for other similar lysosomal enzyme deficiencies. We therefore tested the efficacy of enzyme replacement therapy (ERT) by administering monthly infusions of recombinant human PPT1 (rhPPT1) to PPT1-deficient mice (Cln1–/–) and CLN1R151X sheep to assess how to potentially scale up for translation. In Cln1–/– mice, intracerebrovascular (i.c.v.) rhPPT1 delivery was the most effective route of administration, resulting in therapeutically relevant CNS levels of PPT1 activity. rhPPT1-treated mice had improved motor function, reduced disease-associated pathology, and diminished neuronal loss. In CLN1R151X sheep, i.c.v. infusions resulted in widespread rhPPT1 distribution and positive treatment effects measured by quantitative structural MRI and neuropathology. This study demonstrates the feasibility and therapeutic efficacy of i.c.v. rhPPT1 ERT. These findings represent a key step toward clinical testing of ERT in children with CLN1 disease and highlight the importance of a cross-species approach to developing a successful treatment strategy.
Keywords	Neuroscience ; Therapeutics ; Medicine ; R
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	American Society for Clinical Investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A novel chemotaxis assay in 3-D collagen gels by time-lapse microscopy.

Angela Vasaturo / Sergio Caserta / Ilaria Russo / Valentina Preziosi / Carolina Ciacci / Stefano Guido

PLoS ONE, Vol 7, Iss 12, p e

2012 Volume 52251

Abstract: The directional cell response to chemical gradients, referred to as chemotaxis, plays an important role in physiological and pathological processes including development, immune response and tumor cell invasion. Despite such implications, chemotaxis ... ...

Abstract	The directional cell response to chemical gradients, referred to as chemotaxis, plays an important role in physiological and pathological processes including development, immune response and tumor cell invasion. Despite such implications, chemotaxis remains a challenging process to study under physiologically-relevant conditions in-vitro, mainly due to difficulties in generating a well characterized and sustained gradient in substrata mimicking the in-vivo environment while allowing dynamic cell imaging. Here, we describe a novel chemotaxis assay in 3D collagen gels, based on a reusable direct-viewing chamber in which a chemoattractant gradient is generated by diffusion through a porous membrane. The diffusion process has been analysed by monitoring the concentration of FITC-labelled dextran through epifluorescence microscopy and by comparing experimental data with theoretical and numerical predictions based on Fick's law. Cell migration towards chemoattractant gradients has been followed by time-lapse microscopy and quantified by cell tracking based on image analysis techniques. The results are expressed in terms of chemotactic index (I) and average cell velocity. The assay has been tested by comparing the migration of human neutrophils in isotropic conditions and in the presence of an Interleukin-8 (IL-8) gradient. In the absence of IL-8 stimulation, 80% of the cells showed a velocity ranging from 0 to 1 µm/min. However, in the presence of an IL-8 gradient, 60% of the cells showed an increase in velocity reaching values between 2 and 7 µm/min. Furthermore, after IL-8 addition, I increased from 0 to 0.25 and 0.25 to 0.5, respectively, for the two donors examined. These data indicate a pronounced directional migration of neutrophils towards the IL-8 gradient in 3D collagen matrix. The chemotaxis assay described here can be adapted to other cell types and may serve as a physiologically relevant method to study the directed locomotion of cells in a 3D environment in response to different chemoattractants.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A new method to improve the clinical evaluation of cystic fibrosis patients by mucus viscoelastic properties.

Giovanna Tomaiuolo / Giulia Rusciano / Sergio Caserta / Antonio Carciati / Vincenzo Carnovale / Pasquale Abete / Antonio Sasso / Stefano Guido

PLoS ONE, Vol 9, Iss 1, p e

2014 Volume 82297

Abstract: In cystic fibrosis (CF) patients airways mucus shows an increased viscoelasticity due to the concentration of high molecular weight components. Such mucus thickening eventually leads to bacterial overgrowth and prevents mucus clearance. The altered ... ...

Abstract	In cystic fibrosis (CF) patients airways mucus shows an increased viscoelasticity due to the concentration of high molecular weight components. Such mucus thickening eventually leads to bacterial overgrowth and prevents mucus clearance. The altered rheological behavior of mucus results in chronic lung infection and inflammation, which causes most of the cases of morbidity and mortality, although the cystic fibrosis complications affect other organs as well. Here, we present a quantitative study on the correlation between cystic fibrosis mucus viscoelasticity and patients clinical status. In particular, a new diagnostic parameter based on the correlation between CF sputum viscoelastic properties and the severity of the disease, expressed in terms of FEV1 and bacterial colonization, was developed. By using principal component analysis, we show that the types of colonization and FEV1 classes are significantly correlated to the elastic modulus, and that the latter can be used for CF severity classification with a high predictive efficiency (88%). The data presented here show that the elastic modulus of airways mucus, given the high predictive efficiency, could be used as a new clinical parameter in the prognostic evaluation of cystic fibrosis.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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