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Marine invertebrates produce a plethora of bioactive compounds, which serve as inspiration for marine biotechnology, particularly in drug discovery programs and biomaterials development. This review aims to summarize the potential of drugs derived from marine invertebrates in the field of neuroscience. Therefore, some examples of neuroprotective drugs and neurotoxins will be discussed. Their role in neuroscience research and development of new therapies targeting the central nervous system will be addressed, with particular focus on neuroinflammation and neurodegeneration. In addition, the neuronal growth promoted by marine drugs, as well as the recent advances in neural tissue engineering, will be highlighted. ; The authors are grateful to the financial support from the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundação para a Ciência e Tecnologia) through project Pest-C/EQB/LA0006/2013 and from the European Union (FEDER funds) under the framework of QREN through Project NORTE-07–0124-FEDER-000069, to CYTED Programme (Ref. 112RT0460) CORNUCOPIA Thematic Network and project AGL2011–23690 (CICYT). Clara Grosso thanks FCT for the Post-Doc fellowship (SFRH/BPD/63922/2009). We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI) ; Peer reviewed

Five agarose types (D1LE, D2LE, LM, MS8 and D5) were evaluated in tissue engineering and compared for the first time using an array of analysis methods. Acellular and cellular constructs were generated from 0.3–3%, and their biomechanical properties, in vivo biocompatibility (as determined by LIVE/DEAD, WST-1 and DNA release, with n = 6 per sample) and in vivo biocompatibility (by hematological and biochemical analyses and histology, with n = 4 animals per agarose type) were analyzed. Results revealed that the biomechanical properties of each hydrogel were related to the agarose concentration (p < 0.001). Regarding the agarose type, the highest (p < 0.001) Young modulus, stress at fracture and break load were D1LE, D2LE and D5, whereas the strain at fracture was higher in D5 and MS8 at 3% (p < 0.05). All agaroses showed high biocompatibility on human skin cells, especially in indirect contact, with a correlation with agarose concentration (p = 0.0074 for LIVE/DEAD and p = 0.0014 for WST-1) and type, although cell function tended to decrease in direct contact with highly concentrated agaroses. All agaroses were safe in vivo, with no systemic effects as determined by hematological and biochemical analysis and histology of major organs. Locally, implants were partially encapsulated and a pro-regenerative response with abundant M2- type macrophages was found. In summary, we may state that all these agarose types can be safely used in tissue engineering and that the biomechanical properties and biocompatibility were strongly associated to the agarose concentration in the hydrogel and partially associated to the agarose type. These results open the door to the generation of specific agarose-based hydrogels for definite clinical applications such as the human skin, cornea or oral mucosa. ; Hispanagar SA, Burgos, Spain, through CDTI, Ministry of Science and Innovation, Spain, Programa Operativo Plurirregional de Crecimiento Inteligente (CRIN) IDI-20180052 ; ISCIII thorough AES AC17/00013 ; Junta de Andalucía PE-0395-2019 ; Spanish Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+i) from Ministerio de Ciencia, Innovación y Universidades (Instituto de Salud Carlos III) FIS PI17/0391 ; Fondo Europeo de Desarrollo Regional ERDF-FEDER, European Union PI20/0317

Collagens are the most abundant high molecular weight proteins in both invertebrate and vertebrate organisms, including mammals, and possess mainly a structural role, existing different types according with their specific organization in distinct tissues. From this, they have been elected as one of the key biological materials in tissue regeneration approaches. Also, industry is constantly searching for new natural sources of collagen and upgraded methodologies for their production. The most common sources are from bovine and porcine origin, but other ways are making their route, such as recombinant production, but also extraction from marine organisms like fish. Different organisms have been proposed and explored for collagen extraction, allowing the sustainable production of different types of collagens, with properties depending on the kind of organism (and their natural environment) and extraction methodology. Such variety of collagen properties has been further investigated in different ways to render a wide range of applications. The present review aims to shed some light on the contribution of marine collagens for the scientific and technological development of this sector, stressing the opportunities and challenges that they are and most probably will be facing to assume a role as an alternative source for industrial exploitation. ; The authors would like to acknowledge the funding from ERDF through Atlantic Area Transnational Cooperation Programme Project 2011-1/164 MARMED, POCTEP Projects 0330_IBEROMARE_1_P and 0687_NOVOMAR_1_P and from European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreements nr. KBBE-2010-266033-SPECIAL and nr. REGPOT-CT2012-316331-POLARIS. The Portuguese Foundation for Science and Technology is also acknowledged for the Post-Doc fellowship SFRH/BPD/70230/2010 ...

Many cosmetic formulations have collagen as a major component because of its significant benefits as a natural humectant and moisturizer. This industry is constantly looking for innovative, sustainable, and truly efficacious products, so marine collagen based formulations are arising as promising alternatives. A solid description and characterization of this protein is fundamental to guarantee the highest quality of each batch. In the present study, we present an extensive characterization of marine-derived collagen extracted from salmon and codfish skins, targeting its inclusion as component in cosmetic formulations. Chemical and physical characterizations were performed using several techniques such as sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), Fourier Transformation Infrared (FTIR) spectroscopy rheology, circular dichroism, X-ray diffraction, humidity uptake, and a biological assessment of the extracts regarding their irritant potential. The results showed an isolation of type I collagen with high purity but with some structural and chemical differences between sources. Collagen demonstrated a good capacity to retain water, thus being suitable for dermal applications as a moisturizer. A topical exposure of collagen in a human reconstructed dermis, as well as the analysis of molecular markers for irritation and inflammation, exhibited no irritant potential. Thus, the isolation of collagen from fish skins for inclusion in dermocosmetic applications may constitute a sustainable and low-cost platform for the biotechnological valorization of fish by-products. ; The authors would like to acknowledge to European Union for the financial support under the scope of European Regional Development Fund (ERDF) through the projects 0687_NOVOMAR_1_P (POCTEP (Programa Operacional de Cooperação Transfronteiriça España-Portugal) 2007/2013) and 0302_CVMAR_I_1_P (POCTEP 2014/2020) and the Structured Project NORTE-01-0145-FEDER-000021 (Norte2020) and under the scope of the European Union Seventh ...

The high prevalence of bone defects has become a worldwide problem. Despite the significant amount of research on the subject, the available therapeutic solutions lack efficiency. Autografts, the most commonly used approaches to treat bone defects, have limitations such as donor site morbidity, pain and lack of donor site. Marine resources emerge as an attractive alternative to extract bioactive compounds for further use in bone tissue-engineering approaches. On one hand they can be isolated from by-products, at low cost, creating value from products that are considered waste for the fish transformation industry. One the other hand, religious constraints will be avoided. We isolated two marine origin materials, collagen from shark skin (Prionace glauca) and calcium phosphates from the teeth of two different shark species (Prionace glauca and Isurus oxyrinchus), and further proposed to mix them to produce 3D composite structures for hard tissue applications. Two crosslinking agents, 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride/N-Hydroxysuccinimide (EDC/NHS) and hexamethylene diisocyanate (HMDI), were tested to enhance the scaffolds' properties, with EDC/NHS resulting in better properties. The characterization of the structures showed that the developed composites could support attachment and proliferation of osteoblast-like cells. A promising scaffold for the engineering of bone tissue is thus proposed, based on a strategy of marine by-products valorisation. ; This work was funded by INTERREG under the POCTEP Project 0687_NOVOMAR_1_P and the Atlantic Area Transnational Cooperation Programme Project MARMED (2011-1/164), as well as by European Union FP7 under the project POLARIS (REGPOT-CT2012-316331). The authors gratefully acknowledge the funding support received from European Union through INTERREG—POCTEP Project 0687_NOVOMAR_1_P and Atlantic Area Transnational Cooperation Programme Project MARMED (2011-1/164)—and Research and Development Framework Programme FP7–project POLARIS (REGPOT-CT2012-316331). The authors acknowledge also the Centro Tecnológico del Mar (CETMAR, Vigo, Spain) and COPEMAR SA (fishing company, Spain) for the supply of fish by-products. J.M.S. and R.P. thank FCT respectively for the Post-Doctoral fellowship financed by POPH/FSE (SFRH/BPD/70230/2010) and for the contract IF/00347/2015. G.S.D. thanks Norte2020 by the PhD scholarship (NORTE-08-5369-F SE-000044). ; Peer reviewed

The high prevalence of bone defects has become a worldwide problem. Despite the significant amount of research on the subject, the available therapeutic solutions lack efficiency. Autografts, the most common used approaches to treat bone defects have limitations such as donor site morbidity, pain and lack of donor site. Marine resources emerge as an attractive alternative to extract bioactive compounds for further use in bone tissue engineering approaches. On one hand they can be isolated from by-products, at low costs, creating value from products that are considered waste for the fish transformation industry. One the other hand, religious constraints will be avoided. We isolated two marine origin materials, collagen from shark skin (Prionace glauca) and calcium phosphates from teeth of two different shark species (Prionace glauca and Isurus oxyrinchus), and further proposed to mix them to produce 3D composite structures for hard tissue applications. Two crosslinking agents, EDC/NHS and HMDI, were tested to enhance scaffoldsâ properties, with EDC/NHS resulting in better properties. The characterization of the structures showed that the developed composites could support attachment and proliferation of osteoblast-like cells. A promising scaffold for the engineering of bone tissue is thus proposed, based on a strategy of marine by-products valorisation. ; This work was funded by INTERREG under the POCTEP Project 0687_NOVOMAR_1_P and the Atlantic Area Transnational Cooperation Programme Project MARMED (2011-1/164), as well as by European Union FP7 under the project POLARIS (REGPOT-CT2012-316331). ...

The extraction of collagen from fish skins is being proposed as strategy for valorization of marine origin by-products, being a sustainable alternative to mammal collagen. The method commonly uses solutions of organic acids, but new methodologies are arising, aiming to improve process yields and/or the properties of the resulting products. In this work, skins removed from salt brine Atlantic cod (Gadus morhua) were used to extract collagen, using water acidified with CO2, obtaining an extraction yield of 13.8% (w/w). Acidified water extracted collagen (AWC) presented a total content of proline-like amino acids of 151/1000 residues, with a degree of hydroxylation of 38%, and its SDS-PAGE profile is compatible with type I collagen. Moreover, FTIR, CD and XRD results suggest the presence of preserved triple helix, having a denaturation temperature of 32.3 °C as determined by micro-DSC. AWC exhibited a typical shear thinning behavior, interesting regarding their further processing, namely in jelly-like formulations. Additionally, the presence of AWC in MRC-5 human fibroblasts culture did not affect cell viability, demonstrating the non-cytotoxic behavior. Overall, the results support the efficiency of the proposed approach for collagen extraction and further enable the design of methodologies to address AWC use in biomedical or cosmetic context. ; This work has received funding from European Union, under the scope of European Regional Development Fund (ERDF) through the Structured Project NORTE-01-0145-FEDER000021 (Norte2020) and under the scope of the European Union Seventh Framework Programme (FP7/2007-2013) through grant agreement ERC-2012-ADG 20120216-321266 (ERC Advanced Grant ComplexiTE). The Portuguese Foundation for Science and Technology is also acknowledged for the grant of A.L.A under Doctoral Programme Do* Mar (PD/BD/127995/2016) and for the PhD grant of C. O. (Norte08-5369-000037) with financial support by Norte 2020. The authors would like to acknowledge Frigoríficos da Ermida, Lda. (Gafanha da ...

Collagen is a natural and abundant polymer that serves multiple functions in both invertebrates and vertebrates. As collagen is the natural scaffolding for cells, collagen-based hydrogels are regarded as ideal materials for tissue engineering applications since they can mimic the natural cellular microenvironment. Chondrosia reniformis is a marine demosponge particularly rich in collagen, characterized by the presence of labile interfibrillar crosslinks similarly to those described in the mutable collagenous tissues (MCTs) of echinoderms. As a result single fibrils can be isolated using calcium-chelating and disulphide-reducing chemicals. In the present work we firstly describe a new extraction method that directly produces a highly hydrated hydrogel with interesting self-healing properties. The materials obtained were then biochemically and rheologically characterized. Our investigation has shown that the developed extraction procedure is able to extract collagen as well as other proteins and Glycosaminoglycans (GAG)-like molecules that give the collagenous hydrogel interesting and new rheological properties when compared to other described collagenous materials. The present work motivates further in-depth investigations towards the development of a new class of injectable collagenous hydrogels with tailored specifications. ; The authors gratefully acknowledge the financial support from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement ERC-2012-ADG 20120216-321266 (ERC Advanced Grant project ComplexiTE), as well as from the European Regional Development Fund (ERDF) under the projects "Accelerating tissue engineering and personalized medicine discoveries by the integration of key enabling nanotechonologies, marine-derived biomaterials and stem cells" (NORTE-01-0145-FEDER-000021), supported by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, and 0687_NOVOMAR_1_P, co-financed by transborder cooperation programme POCTEP. The ...

Marine biodiversity is expressed through the huge variety of vertebrate and invertebrate species inhabiting intertidal to deep-sea environments. The extraordinary variety of â forms and functionsâ  exhibited by marine animals suggests they are a promising source of bioactive molecules and provides potential inspiration for different biomimetic approaches. This diversity is familiar to biologists and has led to intensive investigation of metabolites, polysaccharides, and other compounds. However, marine collagens are less well-known. This review will provide detailed insight into the diversity of collagens present in marine species in terms of their genetics, structure, properties, and physiology. In the last part of the review the focus will be on the most common marine collagen sources and on the latest advances in the development of innovative materials exploiting, or inspired by, marine collagens. ; The authors are grateful for the financial support from European Union, under the scope of European Regional Development Fund((ERDF) through the POCTEP project 0687_NOVOMAR_1_P and Structured Project NORTE-01- 0145-FEDER-000021 and from the Portuguese Foundation for Science and Technology (FCT), under the scope of the BiogenInk project (M-ERA-NET2/0022/2016) and from the European Cooperation in Science & Technology program (EU COST). Grant title: "Stem cells of marine/aquatic inverte brates: from basic research to innovative applications" (MARISTEM). MSR acknowledges FCT for the Ph.D. scholarship ...

Collagen is the most abundant protein found in mammals and it exhibits a low immunogenicity, high biocompatibility and biodegradability when compared with others natural polymers. For this reason, it has been explored for the development of biologically instructive biomaterials with applications for tissue substitution and regeneration. Marine origin collagen has been pursued as an alternative to the more common bovine and porcine origins. This study focused on squid (Teuthoidea: Cephalopoda), particularly the Antarctic squid Kondakovia longimana and the Sub-Antarctic squid Illex argentinus as potential collagen sources. In this study, collagen has been isolated fromthe skins of the squids using acid-based and pepsin-based protocols, with the higher yield being obtained from I. argentinus in the presence of pepsin. The produced collagen has been characterized in terms of physicochemical properties, evidencing an amino acid profile similar to the one of calf collagen, but exhibiting a less preserved structure, with hydrolyzed portions and a lower melting temperature. Pepsin-soluble collagen isolated fromI. argentinus was selected for further evaluation of biomedical potential, exploring its incorporation on poly-ε-caprolactone (PCL) 3D printed scaffolds for the development of hybrid scaffolds for tissue engineering, exhibiting hierarchical features. ; This work was partially funded by ERDF through POCTEP Project 0687_NOVOMAR_1_P and by the European Union Seventh Framework Programme for research, technological development and demonstration under grant agreement on ERC-2012-ADG 20120216-321266 (ComplexiTE). The Portuguese Foundation for Science and Technology (FCT) is also acknowledged for post-doctoral fellowships of JMS (SFRH/BPD/70230/2010) and RPP (SFRH/BPD/101886/2014), financed by POPH/FSE, and FCT Investigator grant of JX (IF/00616/2013). The authors also want to thank Dr. Julio Maroto (Fundación CETMAR, Spain) for the kind offer of the samples of skins of I. argentinus, to Dr. Dario Fassini for the ...

This Springer Handbook provides, for the first time, a complete and consistent overview over the methods, applications, and products in the field of marine biotechnology. A large portion of the surface of the earth (ca. 70%) is covered by the oceans. More than 80% of the living organisms on the earth are found in aquatic ecosystems. The aquatic systems thus constitute a rich reservoir for various chemical materials and (bio-)chemical processes.Edited by a renowned expert with a longstanding experience, and including over 60 contributions from leading international scientists, the Springer Handbook of Marine Biotechnology is a major authoritative desk reference for everyone interested or working in the field of marine biotechnology and bioprocessing - from undergraduate and graduate students, over scientists and teachers, to professionals.Marine biotechnology is concerned with the study of biochemical materials and processes from marine sources, that play a vital role in the isolation of novel drugs, and to bring them to industrial and pharmaceutical development. Today, a multitude of bioprocess techniques is employed to isolate and produce marine natural compounds, novel biomaterials, or proteins and enzymes from marine organisms, and to bring them to applications as pharmaceuticals, cosmeceuticals or nutraceuticals, or for the production of bioenergy from marine sources. All these topics are addressed by the Springer Handbook of Marine Biotechnology.The book is divided into ten parts. Each part is consistently organized, so that the handbook provides a sound introduction to marine biotechnology - from historical backgrounds and the fundamentals, over the description of the methods and technology, to their applications - but it can also be used as a reference work.Key topics include: - Marine flora and fauna - Tools and methods in marine biotechnology - Marine genomics - Marine microbiology - Bioenergy and biofuels - Marine bioproducts in industrial applications - Marine bioproducts in medical and pharmaceutical applications - and many more... Prof. Dr. Se-Kwon Kim has more than 40 years of experience as a marine biochemist, working in the field of marine bioprocess and biotechnology. He holds a professorship of marine biochemistry at the Pukyong National University, Pusan, South Korea and is the director of the Marine Bioprocess Research Center in Pusan, Korea. Prof. Kim obtained his PhD from the Pukyong National University, before joining the University of Illinois, Urbana-Champaign (USA) for postdoctoral research. In 1999-2000, he has been visiting professor at the Memorial University of Newfoundland, Canada. To date, his research has been documented in more than 450 original research papers, 76 patents and several books.Prof. Kim's major research interests are bioactive substances derived from marine organisms and their various applications (e.g. as pharmaceuticals, cosmeceuticals, nutraceuticals or for dietary supplements).

Autogenous cancellous bone graft is the current gold standard of treatment for the management of bone defects since it possesses the properties of osteoinduction, osteoconduction, and osteogenesis. Xenografts and synthetic grafts have been widely reported as available and low-cost alternatives, which retain good osteoconductive and mechanical properties. Given the rich biodiversity of ocean organisms, marine sources are of particular interest in the search for alternative bone grafts with enhanced functionalities. The purpose of this paper is to assess the biocompatibility of a marine-derived bone graft obtained from shark tooth, which is an environmentally sustainable and abundant raw material from fishing. This research presents the findings of a preclinical trial—following UNE-EN ISO 10993—that induced a critical-sized bone defect in a rabbit model and compared the results with a commercial bovine-derived bone graft. Evaluation by micro-computed tomography and histomorphometric analysis 12 weeks after implantation revealed good osseointegration, with no signs of inflammatory foreign body reactions, fibrosis, or necrosis in any of the cases. The shark tooth-derived bone graft yielded significantly higher new bone mineral density values (54 ± 6%) than the control (27 ± 8%). Moreover, the percentage of intersection values were much higher (86 ± 8%) than the bovine-derived bone graft (30 ± 1%) used as control. The area of occupancy by bone tissue in the test material (38 ± 5%) also gave higher values than the control (30 ± 6%). The role of physicochemical properties, biphasic structure, and composition on the stimulation of bone regeneration is also discussed ; This research was funded by Xunta de Galicia, grants IN855A 2016/06 (Programa Ignicia–GAIN), ED431C 2017/51 (Competitive Reference Groups) and ED431D 2017/13 (Research networks); and by European Union Interreg Programs, projects IBEROS (0245_IBEROS_1_E, POCTEP 2015), CVMar+i (0302_CVMAR_I_1_P, POCTEP 2015) and BLUEHUMAN (EAPA_151/2016, Atlantic Area 2016) ...

Atlantic cod is processed industrially for food purposes, with several by-products being directed to animal feed and other ends. Looking particularly into swim bladders, the extraction of collagen can be a valuable strategy for by-product valorization, explored in the present work for the first time. Collagen was extracted using acetic acid (ASCsb) and pepsin (PSCsb) with yields of 5.72% (w/w) and 11.14% (w/w), respectively. SDS-PAGE profile showed that the extracts were compatible with type I collagen. FTIR, CD and XRD results suggest that the PSCsb structure underwent partial denaturation, with microDSC showing a band at 54 ºC probably corresponding to a melting process, while ASCsb structure remained intact, with preserved triple helix and a denaturation temperature of 29.6 ºC. Amino acid composition indicates that the total content of proline-like amino acids was 148/1000 residues for ASCsb and 141/1000 residues for PSCsb, with a hydroxylation degree of about 37%. The extracts exhibited a typical shear thinning behavior, interesting property regarding their further processing toward the development of biomaterials. In this regard, assessment of metabolic activity of human fibroblast cells cultured in the presence of collagen extracts with concentrations up to 3mg/mL revealed the absence of cytotoxic behavior. Collagen extracts obtained from Atlantic cod swim bladders shown attractive properties regarding their use in cosmetic or biomedical applications. ; The authors would like to acknowledge to European Union for the financial support under the scope of European Regional Development Fund (ERDF) through the Structured Project NORTE-01-0145-FEDER-000021 (Norte2020) and under the scope of the European Union Seventh Framework Programme (FP7/2007-2013) through grant agreement ERC-2012-ADG 20120216-321266 (ERC Advanced Grant ComplexiTE). The Portuguese Foundation for Science and Technology is also acknowledged for the PhD grant of A. L. A under Doctoral Programme Do ~ Mar (PD/BD/127995/2016), as well as ...

Marine organisms produce a vast diversity of metabolites with biological activities useful for humans, e.g., cytotoxic, antioxidant, anti-microbial, insecticidal, herbicidal, anticancer, pro-osteogenic and pro-regenerative, analgesic, anti-inflammatory, anti-coagulant, cholesterol-lowering, nutritional, photoprotective, horticultural or other beneficial properties. These metabolites could help satisfy the increasing demand for alternative sources of nutraceuticals, pharmaceuticals, cosmeceuticals, food, feed, and novel bio-based products. In addition, marine biomass itself can serve as the source material for the production of various bulk commodities (e.g., biofuels, bioplastics, biomaterials). The sustainable exploitation of marine bio-resources and the development of biomolecules and polymers are also known as the growing field of marine biotechnology. Up to now, over 35,000 natural products have been characterized from marine organisms, but many more are yet to be uncovered, as the vast diversity of biota in the marine systems remains largely unexplored. Since marine biotechnology is still in its infancy, there is a need to create effective, operational, inclusive, sustainable, transnational and transdisciplinary networks with a serious and ambitious commitment for knowledge transfer, training provision, dissemination of best practices and identification of the emerging technological trends through science communication activities. A collaborative (net)work is today compelling to provide innovative solutions and products that can be commercialized to contribute to the circular bioeconomy. This perspective article highlights the importance of establishing such collaborative frameworks using the example of Ocean4Biotech, an Action within the European Cooperation in Science and Technology (COST) that connects all and any stakeholders with an interest in marine biotechnology in Europe and beyond. ; Funding text #1 AR and TR: the publication is part of a project that has received funding from the European Union ...

Huge amounts of chitin and chitosans can be found in the biosphere as important constituents of the exoskeleton of many organisms and as waste by worldwide seafood companies. Presently, politicians, environmentalists, and industrialists encourage the use of these marine polysaccharides as a renewable source developed by alternative eco-friendly processes, especially in the production of regular cosmetics. The aim of this review is to outline the physicochemical and biological properties and the different bioextraction methods of chitin and chitosan sources, focusing on enzymatic deproteinization, bacteria fermentation, and enzymatic deacetylation methods. Thanks to their biodegradability, non-toxicity, biocompatibility, and bioactivity, the applications of these marine polymers are widely used in the contemporary manufacturing of biomedical and pharmaceutical products. In the end, advanced cosmetics based on chitin and chitosans are presented, analyzing different therapeutic aspects regarding skin, hair, nail, and oral care. The innovative formulations described can be considered excellent candidates for the prevention and treatment of several diseases associated with different body anatomical sectors.