scholarly journals Characterization of goat prions demonstrates geographical variation of scrapie strains in Europe and reveals the composite nature of prion strains

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Romolo Nonno ◽  
Alba Marin-Moreno ◽  
Juan Carlos Espinosa ◽  
Christine Fast ◽  
Lucien Van Keulen ◽  
...  
Keyword(s):  
Small Ruminants ◽  
Direct Interaction ◽  
Biological Properties ◽  
Spongiform Encephalopathy ◽  
Strain Diversity ◽  
Wide Range ◽  
Strain Components ◽  
Composite Strain ◽  
Composite Nature ◽  
Scrapie Strains

AbstractBovine Spongiform Encephalopathy (BSE) is the only animal prion which has been recognized as a zoonotic agent so far. The identification of BSE in two goats raised the need to reliably identify BSE in small ruminants. However, our understanding of scrapie strain diversity in small ruminants remains ill-defined, thus limiting the accuracy of BSE surveillance and spreading fear that BSE might lurk unrecognized in goats. We investigated prion strain diversity in a large panel of European goats by a novel experimental approach that, instead of assessing the neuropathological profile after serial transmissions in a single animal model, was based on the direct interaction of prion isolates with several recipient rodent models expressing small ruminants or heterologous prion proteins. The findings show that the biological properties of scrapie isolates display different patterns of geographical distribution in Europe and suggest that goat BSE could be reliably discriminated from a wide range of biologically and geographically diverse goat prion isolates. Finally, most field prion isolates showed composite strain features, with discrete strain components or sub-strains being present in different proportions in individual goats or tissues. This has important implications for understanding the nature and evolution of scrapie strains and their transmissibility to other species, including humans.

scholarly journals Classical scrapie in small ruminants is caused by at least four different prion strains

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Alba Marín-Moreno ◽  
Patricia Aguilar-Calvo ◽  
Juan Carlos Espinosa ◽  
María Zamora-Ceballos ◽  
José Luis Pitarch ◽  
...  
Keyword(s):  
Transmissible Spongiform Encephalopathy ◽  
Small Ruminants ◽  
Classical Scrapie ◽  
Spongiform Encephalopathy ◽  
Rodent Models ◽  
Species Barrier ◽  
Single Strain ◽  
Prion Strains ◽  
Scrapie Strains

AbstractThe diversity of goat scrapie strains in Europe has recently been studied using bioassays in a wide collection of rodent models, resulting in the classification of classical scrapie into four different categories. However, the sole use of the first passage does not lead to isolate adaptation and identification of the strains involved and might therefore lead to misclassification of some scrapie isolates. Therefore, this work reports the complete transmission study of a wide collection of goat transmissible spongiform encephalopathy (TSE) isolates by intracranial inoculation in two transgenic mouse lines overexpressing either small ruminant (TgGoat-ARQ) or bovine (TgBov) PrPC. To compare scrapie strains in sheep and goats, sheep scrapie isolates from different European countries were also included in the study. Once the species barrier phenomenon was overcome, an accurate classification of the isolates was attained. Thus, the use of just two rodent models allowed us to fully differentiate at least four different classical scrapie strains in small ruminants and to identify isolates containing mixtures of strains. This work reinforces the idea that classical scrapie in small ruminants is a prion disease caused by multiple different prion strains and not by a single strain, as is the case for epidemic classical bovine spongiform encephalopathy (BSE-C). In addition, the clear dissimilarity between the different scrapie strains and BSE-C does not support the idea that classical scrapie is the origin of epidemic BSE-C.

Safety assessment of biological raw materials in the system of medicines quality assurance

2020 ◽  
pp. 63-72
Author(s):  
Yu. Olefir ◽  
E. Sakanyan ◽  
I. Osipova ◽  
V. Dobrynin ◽  
M. Smirnova ◽  
...  
Keyword(s):  
Raw Materials ◽  
State Level ◽  
The State ◽  
Spongiform Encephalopathy ◽  
Safety Standards ◽  
Wide Range ◽  
The Russian Federation ◽  
Key Aspects ◽  
First Time ◽  
Medicines Quality

The entry of a wide range of biotechnological products into the pharmaceutical market calls for rein-forcement of the quality, efficacy and safety standards at the state level. The following general monographs have been elaborated for the first time to be included into the State Pharmacopoeia of the Russian Federation, XIV edition: "Viral safety" and "Reduction of the risk of transmitting animal spongiform encephalopathy via medicinal products". These general monographs were elaborated taking into account the requirements of foreign pharmacopoeias and the WHO recommendations. The present paper summarises the key aspects of the monographs.

scholarly journals Advanced mycelium materials as potential self-growing biomedical scaffolds

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Elena Antinori ◽  
Marco Contardi ◽  
Giulia Suarato ◽  
Andrea Armirotti ◽  
Rosalia Bertorelli ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Low Cost ◽  
Direct Interaction ◽  
Dermal Fibroblasts ◽  
Engineering Systems ◽  
Edible Fungi ◽  
Avant Garde ◽  
Fibrous Network ◽  
Body Tissues ◽  
Wide Range

AbstractMycelia, the vegetative part of fungi, are emerging as the avant-garde generation of natural, sustainable, and biodegradable materials for a wide range of applications. They are constituted of a self-growing and interconnected fibrous network of elongated cells, and their chemical and physical properties can be adjusted depending on the conditions of growth and the substrate they are fed upon. So far, only extracts and derivatives from mycelia have been evaluated and tested for biomedical applications. In this study, the entire fibrous structures of mycelia of the edible fungi Pleurotus ostreatus and Ganoderma lucidum are presented as self-growing bio-composites that mimic the extracellular matrix of human body tissues, ideal as tissue engineering bio-scaffolds. To this purpose, the two mycelial strains are inactivated by autoclaving after growth, and their morphology, cell wall chemical composition, and hydrodynamical and mechanical features are studied. Finally, their biocompatibility and direct interaction with primary human dermal fibroblasts are investigated. The findings demonstrate the potentiality of mycelia as all-natural and low-cost bio-scaffolds, alternative to the tissue engineering systems currently in place.

scholarly journals Isobornylchalcones as Scaffold for the Synthesis of Diarylpyrazolines with Antioxidant Activity

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3579
Author(s):  
Svetlana A. Popova ◽  
Evgenia V. Pavlova ◽  
Oksana G. Shevchenko ◽  
Irina Yu. Chukicheva ◽  
Aleksandr V. Kutchin
Keyword(s):  
Antioxidant Activity ◽  
Antioxidant Properties ◽  
Biological Properties ◽  
High Reactivity ◽  
Biologically Active ◽  
Brain Lipids ◽  
Wide Range ◽  
Privileged Structure ◽  
Vitro Model

The pyrazoline ring is defined as a “privileged structure” in medicinal chemistry. A variety of pharmacological properties of pyrazolines is associated with the nature and position of various substituents, which is especially evident in diarylpyrazolines. Compounds with a chalcone fragment show a wide range of biological properties as well as high reactivity which is primarily due to the presence of an α, β-unsaturated carbonyl system. At the same time, bicyclic monoterpenoids deserve special attention as a source of a key structural block or as one of the pharmacophore components of biologically active molecules. A series of new diarylpyrazoline derivatives based on isobornylchalcones with different substitutes (MeO, Hal, NO2, N(Me)2) was synthesized. Antioxidant properties of the obtained compounds were comparatively evaluated using in vitro model Fe2+/ascorbate-initiated lipid peroxidation in the substrate containing brain lipids of laboratory mice. It was demonstrated that the combination of the electron-donating group in the para-position of ring B and OH-group in the ring A in the structure of chalcone fragment provides significant antioxidant activity of synthesized diarylpyrazoline derivatives.

scholarly journals Bioactive potential of natural biomaterials: identification, retention and assessment of biological properties

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kieran Joyce ◽  
Georgina Targa Fabra ◽  
Yagmur Bozkurt ◽  
Abhay Pandit
Keyword(s):  
Tissue Engineering ◽  
Therapeutic Potential ◽  
Biological Properties ◽  
Biological Assessment ◽  
Cross Linking ◽  
Natural Polymers ◽  
Drug Delivery Device ◽  
Biomedical Device ◽  
Wide Range ◽  
Bioactive Potential

AbstractBiomaterials have had an increasingly important role in recent decades, in biomedical device design and the development of tissue engineering solutions for cell delivery, drug delivery, device integration, tissue replacement, and more. There is an increasing trend in tissue engineering to use natural substrates, such as macromolecules native to plants and animals to improve the biocompatibility and biodegradability of delivered materials. At the same time, these materials have favourable mechanical properties and often considered to be biologically inert. More importantly, these macromolecules possess innate functions and properties due to their unique chemical composition and structure, which increase their bioactivity and therapeutic potential in a wide range of applications. While much focus has been on integrating these materials into these devices via a spectrum of cross-linking mechanisms, little attention is drawn to residual bioactivity that is often hampered during isolation, purification, and production processes. Herein, we discuss methods of initial material characterisation to determine innate bioactivity, means of material processing including cross-linking, decellularisation, and purification techniques and finally, a biological assessment of retained bioactivity of a final product. This review aims to address considerations for biomaterials design from natural polymers, through the optimisation and preservation of bioactive components that maximise the inherent bioactive potency of the substrate to promote tissue regeneration.

scholarly journals Hybrid Nanoassemblies from Viruses and DNA Nanostructures

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1413
Author(s):  
Sofia Ojasalo ◽  
Petteri Piskunen ◽  
Boxuan Shen ◽  
Mauri A. Kostiainen ◽  
Veikko Linko
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Dna Nanotechnology ◽  
Biological Properties ◽  
Dna Nanostructures ◽  
Dna Structures ◽  
Nanoscale Structures ◽  
Immune Cell Activation ◽  
Wide Range ◽  
Structural Dna Nanotechnology

Viruses are among the most intriguing nanostructures found in nature. Their atomically precise shapes and unique biological properties, especially in protecting and transferring genetic information, have enabled a plethora of biomedical applications. On the other hand, structural DNA nanotechnology has recently emerged as a highly useful tool to create programmable nanoscale structures. They can be extended to user defined devices to exhibit a wide range of static, as well as dynamic functions. In this review, we feature the recent development of virus-DNA hybrid materials. Such structures exhibit the best features of both worlds by combining the biological properties of viruses with the highly controlled assembly properties of DNA. We present how the DNA shapes can act as “structured” genomic material and direct the formation of virus capsid proteins or be encapsulated inside symmetrical capsids. Tobacco mosaic virus-DNA hybrids are discussed as the examples of dynamic systems and directed formation of conjugates. Finally, we highlight virus-mimicking approaches based on lipid- and protein-coated DNA structures that may elicit enhanced stability, immunocompatibility and delivery properties. This development also paves the way for DNA-based vaccines as the programmable nano-objects can be used for controlling immune cell activation.

Synthesis of 1,2,3–triazole compounds by click chemistry in aqueous medium and evaluation of bactericidal and antitumoral properties.

2021 ◽  
Vol 17 ◽  
Author(s):  
Lucas Lima Zanin ◽  
David Esteban Quintero Jimenez ◽  
Willian Garcia Birolli ◽  
Tiago Venâncio ◽  
Talita Alvarenga Valdes ◽  
...  
Keyword(s):  
Click Chemistry ◽  
Biological Properties ◽  
Antitumoral Activity ◽  
Biological Assays ◽  
Triazole Derivatives ◽  
Optimization Study ◽  
Water As Solvent ◽  
Wide Range ◽  
Screening Study ◽  
High Yields

Background: Triazoles are heterocyclic synthetic compounds that have gained relevance after studies by Sharpless on regioselective methodologies for the synthesis of 1,2,3-triazole derivatives. In addition, they have a wide range of biological properties. Objective: The objective of this study is to develop a synthetic methodology aligned with the principles of click chemistry for the synthesis of 1,2,3-triazole derivatives and verify the profile of these compounds in biological assays. Methods: Initially, a model reaction was selected and an optimization study involving synthetic conditions was carried out. Using the most efficient condition, a series of compounds was developed by the reactions between 2-azido-1-phenylethan-1-one derivatives and terminal alkynes. In sequence, bactericidal and antitumoral assays were performed. Results: It was possible to synthesise ten examples using water as a sustainable solvent, in 1 hour, with good yields of 73–99%, including three compounds described for the first time. Two products presented bactericidal activity, one against the gram-negative Escherichia coli ATCC 25922 and other against the gram-positive Paenibacillus alvei CBMAI 2221. Moreover, other two triazole derivatives presented antitumoral activity for prostate and pancreas cancer cells in this screening study with the bioactivity quantified for compound 1-([1,1'-biphenyl]-4-yl)-2-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)ethan-1-one (IC50 = 132 µM). Conclusion: Herein, an efficient methodology for the synthesis of 1,2,3-triazole derivatives with high yields and using water as solvent was developed. Furthermore, some compounds presented positive results to bactericidal and antitumoral assays, justifying further exploration of these novel compounds and their biological properties.

scholarly journals Novel Trifluoromethyl Pyrimidinone Compounds With Activity Against Mycobacterium tuberculosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Erik Hembre ◽  
Julie V. Early ◽  
Joshua Odingo ◽  
Catherine Shelton ◽  
Olena Anoshchenko ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Major Change ◽  
Structural Features ◽  
Research Area ◽  
Biological Properties ◽  
Pyridyl Ring ◽  
Pyridyl Group ◽  
Gram Positive Bacteria ◽  
Wide Range ◽  
Cytotoxic Molecules

The identification and development of new anti-tubercular agents are a priority research area. We identified the trifluoromethyl pyrimidinone series of compounds in a whole-cell screen against Mycobacterium tuberculosis. Fifteen primary hits had minimum inhibitory concentrations (MICs) with good potency IC90 is the concentration at which M. tuberculosis growth is inhibited by 90% (IC90 < 5 μM). We conducted a structure–activity relationship investigation for this series. We designed and synthesized an additional 44 molecules and tested all analogs for activity against M. tuberculosis and cytotoxicity against the HepG2 cell line. Substitution at the 5-position of the pyrimidinone with a wide range of groups, including branched and straight chain alkyl and benzyl groups, resulted in active molecules. Trifluoromethyl was the preferred group at the 6-position, but phenyl and benzyl groups were tolerated. The 2-pyridyl group was required for activity; substitution on the 5-position of the pyridyl ring was tolerated but not on the 6-position. Active molecules from the series demonstrated low selectivity, with cytotoxicity against eukaryotic cells being an issue. However, there were active and non-cytotoxic molecules; the most promising molecule had an MIC (IC90) of 4.9 μM with no cytotoxicity (IC50 > 100 μM). The series was inactive against Gram-negative bacteria but showed good activity against Gram-positive bacteria and yeast. A representative molecule from this series showed rapid concentration-dependent bactericidal activity against replicating M. tuberculosis bacilli with ~4 log kill in <7 days. Overall the biological properties were promising, if cytotoxicity could be reduced. There is scope for further medicinal chemistry optimization to improve the properties without major change in structural features.

scholarly journals Characterization of an Insoluble and Soluble Form of Melanin Produced by Streptomyces cavourensis SV 21, a Sea Cucumber Associated Bacterium

Marine Drugs ◽  
2022 ◽  
Vol 20 (1) ◽  
pp. 54
Author(s):  
Joko Tri Wibowo ◽  
Matthias Y. Kellermann ◽  
Lars-Erik Petersen ◽  
Yustian R. Alfiansah ◽  
Colleen Lattyak ◽  
...  
Keyword(s):  
Biological Properties ◽  
Water Soluble ◽  
Soluble Form ◽  
Wide Range ◽  
Biological Form ◽  
Insoluble Form ◽  
New Perspective ◽  
Living Organisms ◽  
Purification Protocol

Melanin is a widely distributed and striking dark-colored pigment produced by countless living organisms. Although a wide range of bioactivities have been recognized, there are still major constraints in using melanin for biotechnological applications such as its fragmentary known chemical structure and its insolubility in inorganic and organic solvents. In this study, a bacterial culture of Streptomyces cavourensis SV 21 produced two distinct forms of melanin: (1) a particulate, insoluble form as well as (2) a rarely observed water-soluble form. The here presented novel, acid-free purification protocol of purified particulate melanin (PPM) and purified dissolved melanin (PDM) represents the basis for an in-depth comparison of their physicochemical and biological properties, which were compared to the traditional acid-based precipitation of melanin (AM) and to a synthetic melanin standard (SM). Our data show that the differences in solubility between PDM and PPM in aqueous solutions may be a result of different adjoining cation species, since the soluble PDM polymer is largely composed of Mg2+ ions and the insoluble PPM is dominated by Ca2+ ions. Furthermore, AM shared most properties with SM, which is likely attributed to a similar, acid-based production protocol. The here presented gentler approach of purifying melanin facilitates a new perspective of an intact form of soluble and insoluble melanin that is less chemical altered and thus closer to its original biological form.

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