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Research Project
Aquaculture meets Biomedicine: Innovation in Skeletal Health research.
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Exploring Omega-3′s impact on the expression of Bone-Related Genes in Meagre (Argyrosomus regius)
Publication . Luján-Amoraga, Leticia; Delgado-Martín, Belén; Lourenço-Marques, Cátia; J. Gavaia, Paulo; Bravo, Jimena; Bandarra, Narcisa M.; Dominguez, David; Izquierdo, Marisol S.; Pousão-Ferreira, Pedro; Ribeiro, Laura
Dietary supplementation with Omega-3 fatty acids seems to promote skeletal health. Therefore, their consumption at imbalanced or excessive levels has offered less beneficial or even prejudicial
effects. Fish produced in aquaculture regimes are prone to develop abnormal skeletons. Although
larval cultures are usually fed with diets supplemented with Omega-3 Long Chain Polyunsaturated
fatty acids (LC-PUFAs), the lack of knowledge about the optimal requirements for fatty acids or about
their impact on mechanisms that regulate skeletal development has impeded the design of diets that
could improve bone formation during larval stages when the majority of skeletal anomalies appear. In
this study, Argyrosomus regius larvae were fed different levels of Omega-3s (2.6% and 3.6% DW on diet)
compared to a commercial diet. At 28 days after hatching (DAH), their transcriptomes were analyzed
to study the modulation exerted in gene expression dynamics during larval development and identify
impacted genes that can contribute to skeletal formation. Mainly, both levels of supplementation
modulated bone-cell proliferation, the synthesis of bone components such as the extracellular matrix,
and molecules involved in the interaction and signaling between bone components or in important
cellular processes. The 2.6% level impacted several genes related to cartilage development, denoting
a special impact on endochondral ossification, delaying this process. However, the 3.6% level seemed
to accelerate this process by enhancing skeletal development. These results offered important insights
into the impact of dietary Omega-3 LC-PUFAs on genes involved in the main molecular mechanism
and cellular processes involved in skeletal development.
The essentials of Marine Biotechnology
Publication . Rotter, Ana; Barbier, Michéle; Bertoni, Francesco; Bones, Atle M.; Cancela, M. Leonor; Carlsson, Jens; Carvalho, Maria F.; Cegłowska, Marta; Chirivella-Martorell, Jerónimo; Conk Dalay, Meltem; Cueto, Mercedes; Dailianis, Thanos; Deniz, Irem; Díaz-Marrero, Ana R.; Drakulovic, Dragana; Dubnika, Arita; Edwards, Christine; Einarsson, Hjörleifur; Erdoǧan, Ayşegül; Eroldoǧan, Orhan Tufan; Ezra, David; Fazi, Stefano; FitzGerald, Richard J.; Gargan, Laura M.; Gaudêncio, Susana P.; Gligora Udovič, Marija; Ivošević DeNardis, Nadica; Jónsdóttir, Rósa; Kataržytė, Marija; Klun, Katja; Kotta, Jonne; Ktari, Leila; Ljubešić, Zrinka; Lukić Bilela, Lada; Mandalakis, Manolis; Massa-Gallucci, Alexia; Matijošytė, Inga; Mazur-Marzec, Hanna; Mehiri, Mohamed; Nielsen, Søren Laurentius; Novoveská, Lucie; Overlingė, Donata; Perale, Giuseppe; Ramasamy, Praveen; Rebours, Céline; Reinsch, Thorsten; Reyes, Fernando; Rinkevich, Baruch; Robbens, Johan; Röttinger, Eric; Rudovica, Vita; Sabotič, Jerica; Safarik, Ivo; Talve, Siret; Tasdemir, Deniz; Theodotou Schneider, Xenia; Thomas, Olivier P.; Toruńska-Sitarz, Anna; Varese, Giovanna Cristina; Vasquez, Marlen I.
Coastal countries have traditionally relied on the existing marine resources (e.g., fishing,
food, transport, recreation, and tourism) as well as tried to support new economic
endeavors (ocean energy, desalination for water supply, and seabed mining). Modern
societies and lifestyle resulted in an increased demand for dietary diversity, better health
and well-being, new biomedicines, natural cosmeceuticals, environmental conservation,
and sustainable energy sources. These societal needs stimulated the interest of
researchers on the diverse and underexplored marine environments as promising and
sustainable sources of biomolecules and biomass, and they are addressed by the
emerging field of marine (blue) biotechnology. Blue biotechnology provides opportunities
for a wide range of initiatives of commercial interest for the pharmaceutical, biomedical,
cosmetic, nutraceutical, food, feed, agricultural, and related industries. This article
synthesizes the essence, opportunities, responsibilities, and challenges encountered in
marine biotechnology and outlines the attainment and valorization of directly derived
or bio-inspired products from marine organisms. First, the concept of bioeconomy is
introduced. Then, the diversity of marine bioresources including an overview of the most
prominent marine organisms and their potential for biotechnological uses are described.
This is followed by introducing methodologies for exploration of these resources and
the main use case scenarios in energy, food and feed, agronomy, bioremediation
and climate change, cosmeceuticals, bio-inspired materials, healthcare, and well-being
sectors. The key aspects in the fields of legislation and funding are provided, with the
emphasis on the importance of communication and stakeholder engagement at all
levels of biotechnology development. Finally, vital overarching concepts, such as the
quadruple helix and Responsible Research and Innovation principle are highlighted as
important to follow within the marine biotechnology field. The authors of this review
are collaborating under the European Commission-funded Cooperation in Science and
Technology (COST) Action Ocean4Biotech – European transdisciplinary networking
platform for marine biotechnology and focus the study on the European state of affairs.
The osteogenic and mineralogenic potential of the microalgae Skeletonema costatum and Tetraselmis striata CTP4 in fish models
Publication . Carletti, Alessio; Rosa, Joana; Pes, Katia; Borges, Inês; Santos, Tamara; Barreira, Luísa; Varela, João; Pereira, Hugo; Cancela, M. Leonor; J. Gavaia, Paulo; Laizé, Vincent
Skeletal disorders are problematic aspects for the aquaculture industry as skeletal deformities, which affect most species of farmed fish, increase production costs and affect fish welfare. Following recent findings that show the presence of osteoactive compounds in marine organisms, we evaluated the osteogenic and mineralogenic potential of commercially available microalgae strains Skeletonema costatum and Tetraselmis striata CTP4 in several fish systems. Ethanolic extracts increased extracellular matrix mineralization in gilthead seabream (Sparus aurata) bone-derived cell cultures and promoted osteoblastic differentiation in zebrafish (Danio rerio) larvae. Long-term dietary exposure to both extracts increased bone mineralization in zebrafish and upregulated the expression of genes involved in bone formation (sp7, col1a1a, oc1, and oc2), bone remodeling (acp5a), and antioxidant defenses (cat, sod1). Extracts also improved the skeletal status of zebrafish juveniles by reducing the incidence of skeletal anomalies. Our results indicate that both strains of microalgae contain osteogenic and mineralogenic compounds, and that ethanolic extracts have the potential for an application in the aquaculture sector as dietary supplements to support fish bone health. Future studies should also identify osteoactive compounds and establish whether they can be used in human health to broaden the therapeutic options for bone erosive disorders such as osteoporosis.
Reversal of doxorubicin-Induced bone loss and mineralization by supplementation of Resveratrol and MitoTEMPO in the early development of Sparus aurata
Publication . Poudel, Sunil; Izquierdo, Marisol; Cancela, M. Leonor; Gavaia, Paulo
Doxorubicin is a widely used chemotherapeutic drug known to induce bone loss. The mechanism behind doxorubicin-mediated bone loss is unclear, but oxidative stress has been suggested as a potential cause. Antioxidants that can counteract the toxic effect of doxorubicin on the bone would be helpful for the prevention of secondary osteoporosis. We used resveratrol, a natural antioxidant, and MitoTEMPO, a mitochondria-targeted antioxidant, to counteract doxorubicin-induced bone loss and mineralization on Sparus aurata larvae. Doxorubicin supplemented Microdiets increased bone deformities, decreased mineralization, and lipid peroxidation, whereas Resveratrol and MitoTEMPO supplemented microdiets improved mineralization, decreased bone deformities, and reversed the effects of doxorubicin in vivo and in vitro, using osteoblastic VSa13 cells. Partial Least-Squares Discriminant Analysis highlighted differences between groups on the distribution of skeletal anomalies and mineralization of skeleton elements. Calcium and Phosphorus content was negatively affected in the doxorubicin supplemented group. Doxorubicin reduced the mRNA expression of antioxidant genes, including catalase, glutathione peroxidase 1, superoxide dismutase 1, and hsp90 suggesting that ROS are central for Doxorubicin-induced bone loss. The mRNA expression of antioxidant genes was significantly increased on resveratrol alone or combined treatment. The length of intestinal villi was increased in response to antioxidants and reduced on doxorubicin. Antioxidant supplements effectively prevent bone deformities and mineralization defects, increase antioxidant response and reverse doxorubicin-induced effects on bone anomalies, mineralization, and oxidative stress. A combined treatment of doxorubicin and antioxidants was beneficial in fish larvae and showed the potential for use in preventing Doxorubicin-induced bone impairment.
Antioxidant and anti-inflammatory extracts from sea cucumbers and tunicates induce a pro-osteogenic effect in Zebrafish Larvae
Publication . Carletti, Alessio; Cardoso, Carlos; Lobo-Arteaga, Jorge; Sales, Sabrina; Juliao, Diana; Ferreira, Inês; Chainho, Paula; Dionísio, Maria Ana; Gaudêncio, Maria J.; Afonso, Cláudia; Lourenço, Helena; Cancela, M. Leonor; Bandarra, Narcisa M.; J. Gavaia, Paulo
Bone metabolic disorders such as osteoporosis are characterized by the loss of mineral from the bone tissue leading to its structural weakening and increased susceptibility to fractures. A growing body of evidence suggests that inflammation and oxidative stress play an important role in the pathophysiological processes involved in the rise of these conditions. As the currently available therapeutic strategies are often characterized by toxic effects associated with their long-term use, natural antioxidants and anti-inflammatory compounds such as polyphenols promise to be a valuable alternative for the prevention and treatment of these disorders. In this scope, the marine environment is becoming an important source of bioactive compounds with potential pharmacological applications. Here, we explored the bioactive potential of three species of holothurians (Echinodermata) and four species of tunicates (Chordata) as sources of antioxidant and anti-inflammatory compounds with a particular focus on polyphenolic substances. Hydroethanolic and aqueous extracts were obtained from animals' biomass and screened for their content of polyphenols and their antioxidant and anti-inflammatory properties. Hydroethanolic fractions of three species of tunicates displayed high polyphenolic content associated with strong antioxidant potential and anti-inflammatory activity. Extracts were thereafter tested for their capacity to promote bone formation and mineralization by applying an assay that uses the developing operculum of zebrafish (Danio rerio) to assess the osteogenic activity of compounds. The same three hydroethanolic fractions from tunicates were characterized by a strong in vivo osteogenic activity, which positively correlated with their anti-inflammatory potential as measured by COX-2 inhibition. This study highlights the therapeutic potential of polyphenol-rich hydroethanolic extracts obtained from three species of tunicates as a substrate for the development of novel drugs for the treatment of bone disorders correlated to oxidative stress and inflammatory processes.
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Funding agency
European Commission
Funding programme
H2020
Funding Award Number
766347