Co-designing sustainable biochar business models with sub-Saharan African communities for inclusive socio-economic transformation.

Smallholder farmers in sub-Saharan Africa (SSA) encounter multiple livelihood challenges. Embracing circular bioeconomy principles, particularly considering agricultural and food processing residues, could enable inclusive, locally led, sustainable development pathways within rural communities. Biochar products are one such example of a bio-based material that can be generated using circular principles and deployed for sustainable community development, including among smallholder farmers. This research leverages empirical evidence from four SSA regions to explore the potential of inclusive and sustainable biochar business models, namely: (i) Northern Region, Ghana, (ii) Yamoussoukro, Côte d'Ivoire, (iii) Casamance, Senegal, and (iv) Western Region, Uganda. Co-creation workshops using the Triple-Layered Business Model Canvas framework were carried out in each region with local stakeholders to evaluate the social, ecological, and economic implications of four locally relevant biochar applications: water filtration, biogas purification, soil amendment, and cooking fuel briquettes. Data was analysed at an aggregate level for all regions and applications. The study describes this consolidated biochar business model and examines the implications for SSA communities. The resulting sustainable bio-based business model can guide value chain actors and policymakers in SSA communities towards rural sustainable development with a better understanding of the needs, opportunities, challenges, and impacts of biochar-based value chain development.

Development of a Novel Marine-Derived Tricomposite Biomaterial for Bone Regeneration.

Bone tissue engineering is a promising treatment for bone loss that requires a combination of porous scaffold and osteogenic cells. The aim of this study was to evaluate and develop a tricomposite, biomimetic scaffold consisting of marine-derived biomaterials, namely, chitosan and fucoidan with hydroxyapatite (HA). The effects of chitosan, fucoidan and HA individually and in combination on the proliferation and differentiation of human mesenchymal stem cells (MSCs) were investigated. According to the SEM results, the tricomposite scaffold had a uniform porous structure, which is a key requirement for cell migration, proliferation and vascularisation. The presence of HA and fucoidan in the chitosan tricomposite scaffold was confirmed using FTIR, which showed a slight decrease in porosity and an increase in the density of the tricomposite scaffold compared to other formulations. Fucoidan was found to inhibit cell proliferation at higher concentrations and at earlier time points when applied as a single treatment, but this effect was lost at later time points. Similar results were observed with HA alone. However, both HA and fucoidan increased MSC mineralisation as measured by calcium deposition. Differentiation was significantly enhanced in MSCs cultured on the tricomposite, with increased alkaline phosphatase activity on days 17 and 25. In conclusion, the tricomposite is biocompatible, promotes osteogenesis, and has the structural and compositional properties required of a scaffold for bone tissue engineering. This biomaterial could provide an effective treatment for small bone defects as an alternative to autografts or be the basis for cell attachment and differentiation in ex vivo bone tissue engineering.

Effect of Marine-Derived Saccharides on Human Skin Fibroblasts and Dermal Papilla Cells.

The skin is the largest organ of the human body, composed of a diverse range of cell types, non-cellular components, and an extracellular matrix. With aging, molecules that are part of the extracellular matrix undergo qualitative and quantitative changes and the effects, such as a loss of skin firmness or wrinkles, can be visible. The changes caused by the aging process do not only affect the surface of the skin, but also extend to skin appendages such as hair follicles. In the present study, the ability of marine-derived saccharides, L-fucose and chondroitin sulphate disaccharide, to support skin and hair health and minimize the effects of intrinsic and extrinsic aging was investigated. The potential of the tested samples to prevent adverse changes in the skin and hair through stimulation of natural processes, cellular proliferation, and production of extracellular matrix components collagen, elastin, or glycosaminoglycans was investigated. The tested compounds, L-fucose and chondroitin sulphate disaccharide, supported skin and hair health, especially in terms of anti-aging effects. The obtained results indicate that both ingredients support and promote the proliferation of dermal fibroblasts and dermal papilla cells, provide cells with a supply of sulphated disaccharide GAG building blocks, increase ECM molecule production (collagen and elastin) by HDFa, and support the growth phase of the hair cycle (anagen).

Green Biorefinery systems for the production of climate-smart sustainable products from grasses, legumes and green crop residues.

Grasses, legumes and green plant wastes represent a ubiquitous feedstock for developing a bioeconomy in regions across Europe. These feedstocks are often an important source of ruminant feed, although much remains unused or underutilised. In addition to proteins, these materials are rich in fibres, sugars, minerals and other components that could also be used as inputs for bio-based product development. Green Biorefinery processes and initiatives are being developed to better capitalise on the potential of these feedstocks to produce sustainable food, feed, materials and energy in an integrated way. Such systems may support a more sustainable primary production sector, enable the valorisation of green waste streams, and provide new business models for farmers. This review presents the current developments in Green Biorefining, focusing on a broad feedstock and product base to include different models of Green Biorefinery. It demonstrates the potential and wide applicability of Green Biorefinery systems, the range of bio-based product opportunities and highlights the way forward for their broader implementation. While the potential for new products is extensive, quality control approval will be required prior to market entry.

Biological Properties and Health-Promoting Functions of Laminarin: A Comprehensive Review of Preclinical and Clinical Studies.

Marine algal species comprise of a large portion of polysaccharides which have shown multifunctional properties and health benefits for treating and preventing human diseases. Laminarin, or ß-glucan, a storage polysaccharide from brown algae, has been reported to have potential pharmacological properties such as antioxidant, anti-tumor, anti-coagulant, anticancer, immunomodulatory, anti-obesity, anti-diabetic, anti-inflammatory, wound healing, and neuroprotective potential. It has been widely investigated as a functional material in biomedical applications as it is biodegradable, biocompatible, and is low toxic substances. The reported preclinical and clinical studies demonstrate the potential of laminarin as natural alternative agents in biomedical and industrial applications such as nutraceuticals, pharmaceuticals, functional food, drug development/delivery, and cosmeceuticals. This review summarizes the biological activities of laminarin, including mechanisms of action, impacts on human health, and reported health benefits. Additionally, this review also provides an overview of recent advances and identifies gaps and opportunities for further research in this field. It further emphasizes the molecular characteristics and biological activities of laminarin in both preclinical and clinical settings for the prevention of the diseases and as potential therapeutic interventions.

Switching to Biobased Products - The Brand Owner Perspective.

Brand owners can play a key role in enabling biobased products to penetrate mass markets and to influence consumer choices in relation to biobased products. The current paper explores the role that brand owners can play in supporting market uptake of biobased products and captures the perspectives of European brand owners in relation to biobased products. Based on the findings of this paper, brand owners have an overall positive outlook towards biobased products, with 85% of brands who don't currently use biobased ingredients or products within their branded products and 95% of brands who don't currently use biobased packaging interested in including these in future. However, brand owners still perceive some concerns surrounding biobased products including their high cost, functional performance and ease of integration, as well as their reliability of supply. Regional differences among brand owners have also been identified, with cost and uncertainty around customer demand appearing as a bigger issue in continental Europe, with functional performance concerns appearing as a more pressing issue for brands in northern Europe.

Correction: Griffith, D.M., et al. Novel Improved Synthesis of HSP70 Inhibitor, Pifithrin-µ. In Vitro Synergy Quantification of Pifithrin-µ Combined with Pt Drugs in Prostate and Colorectal Cancer Cells. Molecules 2016, 21, 949.

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Novel Improved Synthesis of HSP70 Inhibitor, Pifithrin-µ. In Vitro Synergy Quantification of Pifithrin-µ Combined with Pt Drugs in Prostate and Colorectal Cancer Cells.

We describe a novel improved approach to the synthesis of the important and well-known heat shock protein 70 inhibitor (HSP70), pifithrin-µ, with corresponding and previously unreported characterisation. The first example of a combination study comprising HSP70 inhibitor pifithrin-µ and cisplatin or oxaliplatin is reported. We have determined, using the Chou-Talalay method, (i) moderate synergistic and synergistic effects in co-treating PC-3 prostate cancer cells with pifithrin-µ and cisplatin and (ii) significant synergistic effects including strong synergism in cotreating HT29 colorectal cancer cells with oxaliplatin and pifithrin-µ.

Development of strategies for conditional RNA interference.

BACKGROUND: RNA interference (RNAi) represents a powerful tool with which to undertake sequence-dependent suppression of gene expression. Synthesized double-stranded RNA (dsRNA) or dsRNA generated endogenously from plasmid or viral vectors can be used for RNAi. For the latter, polymerase III promoters which drive ubiquitous expression in all tissues have typically been adopted. Given that dsRNA molecules must contain few 5' and 3' over-hanging bases to maintain potency, employing polymerase II promoters to drive tissue-specific expression of RNAi may be problematic due to potential inclusion of nucleotides 5' and 3' of siRNA sequences. METHODS: To circumvent this, polymerase II promoters in combination with cis-acting hammerhead ribozymes and short-hairpin RNA sequences have been explored as a means to generate potent dsRNA molecules in tissues defined by the promoter in use. RESULTS: The novel constructs evaluated in this study produced functional siRNA which suppressed the enhanced green fluorescent protein (eGFP) both in vitro and in vivo (in mice). Additionally, the constructs did not appear to elicit a significant type-1 interferon response compared to traditional H1-transcribed shRNA. CONCLUSIONS: Given the potential 'off-target' effects of dsRNAs, it would be preferable in many cases to limit expression of dsRNA to the tissue of interest and moreover would significantly augment the resolution of RNAi technologies. Notably, the system under evaluation in this study could readily be adapted to achieve this objective.

RNAi-based suppression and replacement of rds-peripherin in retinal organotypic culture.

Extensive mutational heterogeneity presents a significant barrier to the development of therapeutics for RDS-peripherin-linked autosomal-dominant retinitis pigmentosa (RP), for which more than 50 disease-related mutations have been identified to date. Mutation-independent suppression, using RNA interference (RNAi), together with simultaneous expression of a replacement rds gene (r-rds, which has been altered to escape suppression but nevertheless encodes wild-type protein) has been explored in COS-7 cells and mouse retinal explants. The efficacy of small interfering and short hairpin RNAs (si/shRNAs) silencing mouse rds, and the function of r-rds (containing degenerate substitutions in the RNAi target sequence) were analyzed at transcript (RT-PCR) and protein (ELISA) levels in COS-7 cells. "Dual-" and "triple-expression" constructs carrying the shRNA suppressor and the marker EGFP with or without the r-rds cassette were electroporated in vitro into retinal explants from 1-day-old pups. The retinae were dissociated at day 14, and transduced cells were FACS-sorted using the coexpressed EGFP marker and analyzed by RT-PCR. si/shRNAs decreased rds mRNA and protein expression by up to 82%, while r-rds was protected from suppression in COS-7 cells. Similarly, efficient RNAi-mediated suppression of endogenous rds was detected in retinal explants, while concomitant rescue of r-rds was also achieved. These data validate the concept of RNAi-based suppression coupled with replacement technology for the development of therapies targeting RDS-linked autosomal-dominant RP, and suggest that such approaches could potentially be used for other autosomal-dominant diseases with similarly extensive intragenic heterogeneity.

Emerging therapeutic approaches for osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is an incurable genetic brittle-bone disease. Although drug therapy, surgery and physiotherapy represent current treatments for OI, the search is ongoing for effective and innovative new therapies targeting the underlying causes of the disease. In this regard, recent advances in the fields of gene and stem-cell therapies have been considerable. In spite of the many challenges that remain, potential new therapies for OI, which have been tested in cell culture systems, animal models and patients, offer hope for the future development of successful therapies. Recent progress in the field is reviewed here.

RNAi of COL1A1 in mesenchymal progenitor cells.

Given that mutant COL1A1 is known to cause Osteogenesis Imperfecta (OI), tools to modulate COL1A1 expression are likely to be of significant therapeutic value. In this context, we have evaluated RNA interference (RNAi) as a means to downregulate COL1A1 expression in Cos-7 cells and in human mesenchymal progenitor stem cells (MPCs), the latter cells giving rise to bone and therefore representing a target cell type for collagen-related disorders. In addition, allele-specificity, a key factor to the success of RNAi-based suppression, was explored with a view to developing a mutation-independent RNAi-based therapeutic for OI by targeting an intragenic SNP within transcripts derived from the COL1A1 gene. Preferential suppression of individual polymorphic alleles that differed by a single nucleotide was observed.

Validation in mesenchymal progenitor cells of a mutation-independent ex vivo approach to gene therapy for osteogenesis imperfecta.

Over 100 dominant-negative mutations within the COL1A1 gene have been identified in osteogenesis imperfecta (OI). In terms of human therapeutics, targeting each of these mutations independently is unlikely to be feasible. Here we show that the hammerhead ribozyme Rzpol1a1, targeting a common polymorphism within transcripts from the COL1A1 gene, downregulates COL1A1 transcript in human mesenchymal progenitor cells at a ribozyme to transcript ratio of only 1:1. Downregulation was confirmed at the protein level. Transducing stem cells with Rzpol1A1 ex vivo followed by autologous transplantation could provide a gene therapy for a large proportion of OI patients with gain-of-function mutations using a single therapeutic.