Summary: Xpaths is a collection of algorithms that allow for the prediction of compound-induced molecular mechanisms of action by integrating phenotypic endpoints of different species; and proposes follow-up tests for model organisms to validate these pathway predictions. The Xpaths algorithms are applied to predict developmental and reproductive toxicity (DART) and implemented into an in silico platform, called DARTpaths.
Background: The heat shock protein (HSP) inducer, geranylgeranylacetone (GGA), was previously found to protect against atrial fibrillation (AF) remodeling in experimental model systems. Clinical application of GGA in AF is limited, due to low systemic concentrations owing to the hydrophobic character of GGA.Objectives: To identify novel HSP-inducing compounds, with improved physicochemical properties, that prevent contractile dysfunction in experimental model systems for AF.
From the article: "To enable selection of novel chemicals for new processes, there is a recognized need for alternative toxicity screening assays to assess potential risks to man and the environment. For human health hazard assessment these screening assays need to be translational to humans, have high throughput capability, and from an animal welfare perspective be harmonized with the principles of the 3Rs (Reduction, Refinement, Replacement). In the area of toxicology a number of cell culture systems are available but while these have some predictive value, they are not ideally suited for the prediction of developmental and reproductive toxicology (DART). This is because they often lack biotransformation capacity, multicellular or multi- organ complexity, for example, the hypothalamus pituitary gonad (HPG) axis and the complete life cycle of whole organisms. To try to overcome some of these limitations in this study, we have used Caenorhabditis elegans (nematode) and Danio rerio embryos (zebrafish) as alternative assays for DART hazard assessment of some candidate chemicals being considered for a new commercial application. Nematodes exposed to Piperazine and one of the analogs tested showed a slight delay in development compared to untreated animals but only at high concentrations and with Piperazine as the most sensitive compound. Total brood size of the nematodes was also reduced primarily by Piperazine and one of the analogs. In zebrafish Piperazine and analogs showed developmental delays. Malformations and mortality in individual fish were also scored. Significant malformations were most sensitively identified with Piperazine, significant mortality was only observed in Piperazine and only at the higest dose. Thus, Piperazine seemed the most toxic compound for both nematodes and zebrafish. The results of the nematode and zebrafish studies were in alignment with data obtained from conventional mammalian toxicity studies indicating that these have potential as developmental toxicity screening systems. The results of these studies also provided reassurance that none of the Piperazines tested are likely to have any significant developmental and/or reproductive toxicity issues to humans when used in their commercial applications."
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Chemical preservation is an important process that prevents foods, personal care products, woods and household products, such as paints and coatings, from undesirable change or decomposition by microbial growth. To date, many different chemical preservatives are commercially available, but they are also associated with health threats and severe negative environmental impact. The demand for novel, safe, and green chemical preservatives is growing, and this process is further accelerated by the European Green Deal. It is expected that by the year of 2050 (or even as soon as 2035), all preservatives that do not meet the ‘safe-by-design’ and ‘biodegradability’ criteria are banned from production and use. To meet these European goals, there is a large need for the development of green, circular, and bio-degradable antimicrobial compounds that can serve as alternatives for the currently available biocidals/ preservatives. Anthocyanins, derived from fruits and flowers, meet these sustainability goals. Furthermore, preliminary research at the Hanze University of Applied Science has confirmed the antimicrobial efficacy of rose and tulip anthocyanin extracts against an array of microbial species. Therefore, these molecules have the potential to serve as novel, sustainable chemical preservatives. In the current project we develop a strategy consisting of fractionation and state-of-the-art characterization methods of individual anthocyanins and subsequent in vitro screening to identify anthocyanin-molecules with potent antimicrobial efficacy for application in paints, coatings and other products. To our knowledge this is the first attempt that combines in-depth chemical characterization of individual anthocyanins in relation to their antimicrobial efficacy. Once developed, this strategy will allow us to single out anthocyanin molecules with antimicrobial properties and give us insight in structure-activity relations of individual anthocyanins. Our approach is the first step towards the development of anthocyanin molecules as novel, circular and biodegradable non-toxic plant-based preservatives.
The valorization of biowaste, by exploiting side stream compounds as feedstock for the sustainable production of bio-based materials, is a key step towards a more circular economy. In this regard, chitin is as an abundant resource which is accessible as a waste compound of the seafood industry. From a commercial perspective, chitin is chemically converted into chitosan, which has multiple industrial applications. Although the potential of chitin has long been established, the majority of seafood waste containing chitin is still left unused. In addition, current processes which convert chitin into chitosan are sub-optimal and have a significant impact on the environment. As a result, there is a need for the development of innovative methods producing bio-based products from chitin. This project wants to contribute to these challenges by performing a feasibility study which demonstrates the microbial bioconversion of chitin to polyhydroxyalkanoates (PHAs). Specifically, the consortium will attempt to cultivate and engineer a recently discovered bacterium Chi5, so that it becomes able to directly produce PHAs from chitin present in solid shrimp shell waste. If successful, this project will provide a proof-of-concept for a versatile microbial production platform which can contribute to: i) the valorization of biowaste from the seafood industry, ii) the efficient utilization of chitin as feedstock, iii) the sustainable and (potentially low-cost) production of PHAs. The project consortium is composed of: i) Van Belzen B.V., a Dutch shrimp trading company which are highly interested in the valorization of their waste streams, hereby making their business model more profitable and sustainable. ii) AMIBM, which have recently isolated and characterized the Chi5 marine-based chitinolytic bacterium and iii) Zuyd, which will link aforementioned partners with students in creating a novel collaboration which will stimulate the development of students and the translation of academic knowledge to a feasible application technology for SME’s.
On a yearly basis 120 million kg of spent coffee ground (SCG) is disposed as waste. Two partners in the project have the intension to refine the valuable compounds from this coffee residue. One of these compounds is the group of melanoidins. It is proven that these natural polymers, with polyphenols incorporated, can be applied as colourant to textiles. These colourant compounds can be extracted from the SCG. In this project an industrial feasible dye recipe for SCG extract to cotton will be developed. This twostep dye method consists of a mordanting step and a colour uptake step. Both will be optimised to colour intensity and light and wash fastness. Parameters as cycle time and energy and water consumption, will be take into account to make the dye recipe applicable for industrial standards. Chemical analysis of mordant compounds (tannins) and colourants (polyphenols) will be carried out to quantify and qualify the uptake by cotton. With the results of this project, the partners will be able to support their customers of the SCG extract with a scientific based advise about the application as a textile dye to ensure a solid market acceptance of SCG extract. With the SCG extract as a professional biobased colorant in the market, companies in textile industry will have a wider choice in using environmental friendly products. At the end, this will lead to complete biodegradable products for consumers.
