Recent advances using gold nanoparticles as a promising multimodal tool for tissue engineering and regenerative medicine

Uncorrected proofGold nanoparticles (AuNPs) have arisen a lot of interest in the clinical realms of nanomedicine. Despite the large ad- vances made in cancer research using AuNPs, their use in tissue engineering and regenerative medicine (TERM) is still in its infancy. Herein, it is discussed the properties, functionalization, and emerging use of AuNPs as a multifunctional and multimodal platform for drug delivery, phototherapy, diagnostic and cell imaging purposes. Moreover, the recent reports related to the ability of AuNPs to enhance stem cell differentiation for bone tissue engineering, to enhance the mechanical and adhesive properties of scaffolds and surface topography to guide cell behaviors are addressed.The authors would like to thank QREN (ON.2 – NORTE-01-0124-FEDER-000018) co-financed by North Portugal Regional Operational Program (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF) for providing financial support to this project. The Portuguese Foundation for Science and Technology (FCT) distinction attributed to J.M. Oliveira under the FCT Investigator program (IF/00423/2012) is also greatly acknowledged. The authors also thank the financial support provided under the ERC funded project ComplexiTE (Grant ERC-2012-ADG_20120216-321266)

Gellan-gum coated gold nanorods: a new tool for biomedical applications

Publicado em "Frontiers in Bioengineering and Biotechnology. Conference Abstract: 10th World Biomaterials Congress"Introduction: Gold nanorods (AuNRs) have been widely studied, in the scope of cancer research and biomedical applications [1]. Their optical properties, easy synthesis and high surface area make AuNRs an outstanding tool for a plethora of applications, such as drug delivery, imaging and tissue engineering [2]. However, before biomedical usage, it is necessary to modify AuNRs surface chemistry, to improve their biocompatibility and stability under biological conditions [3]. One possible approach is the use of biocompatible natural-based polymers that enhance AuNRs performance while allowing the controlled release of drugs/bioactive agents. Herein, we report the successful preparation of a core-shell nanostructure using low-acyl gellan gum (GG) [4], [5] for the coating of AuNRs. Methods: AuNRs were prepared following the seed-mediated growth method [6]. Then, particles were coated with a successive deposition of anionic and cationic polyelectrolytes (poly(acrylic acid) and poly(allylamine hydrochloride), respectively). The pre-coated nanorods were added to a low-acyl gellan gum (GG) solution, previously heated at 90ºC to allow dissolution, and the mixture was stirred overnight at room temperature. The GG-coated AuNRs (AuNR-GG) were characterized by UVvisible spectrometry, zeta potential measurements and transmission electron microscopy (TEM). AuNRs cytotoxicity was accessed in vitro after 1, 3, 7 and 14 days of SaOS-2 cell culture, using an MTS assay. Nanoparticles internalization was confirmed by TEM. In vivo biocompatibility tests were also performed by delivering a solution of AuNRs-GG via tail injection in mice. Results and Discussion: AuNRs were successfully synthesized and coated with a GG shell of approximately 7 nm, as shown in Figure 1. The presence of the GG around AuNRs clearly improved particles stability at different salt and pH conditions, as observed by UV-vis spectroscopy. The in vitro studies using SaOS-2 showed that AuNRs-GG are noncytotoxic. TEM analyses have confirmed that nanoparticles are uptaken by cells and aggregate within cytoplasmic vesicles as depicted in Figure 2. Additionally, in vivo tests suggest that AuNRs are harmless for mice after 24 hours. Conclusion: In this study, AuNRs were individually coated with a gellan gum (GG) shell, resulting in nanoparticles with enhanced stability under different salt concentrations and range of pH’s. Thence, one can conclude that the GG present around the nanoparticles acts as a stabilizer, improving AuNRs stability and biocompatibility. AuNRs-GG have shown noteworthy features and a high potential for further use on biomedical applications including intracellular drug delivery and imaging.QREN (ON.2 – NORTE-01-0124-FEDER-000018) co-financed by North Portugal Regional Operational Program (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF)The Portuguese Foundation for Science and Technology (FCT) - SFRH/BD/102710/201

A novel mechanism causing imbalance of mitochondrial fusion and fission in human myopathies.

Mitochondrial dynamics play an important role in cellular homeostasis and a variety of human diseases are linked to its dysregulated function. Here, we describe a 15-year-old boy with a novel disease caused by altered mitochondrial dynamics. The patient was the second child of consanguineous Jewish parents. He developed progressive muscle weakness and exercise intolerance at 6 years of age. His muscle biopsy revealed mitochondrial myopathy with numerous ragged red and cytochrome c oxidase (COX) negative fibers and combined respiratory chain complex I and IV deficiency. MtDNA copy number was elevated and no deletions of the mtDNA were detected in muscle DNA. Whole exome sequencing identified a homozygous nonsense mutation (p.Q92*) in the MIEF2 gene encoding the mitochondrial dynamics protein of 49 kDa (MID49). Immunoblotting revealed increased levels of proteins promoting mitochondrial fusion (MFN2, OPA1) and decreased levels of the fission protein DRP1. Fibroblasts of the patient showed elongated mitochondria, and significantly higher frequency of fusion events, mtDNA abundance and aberrant mitochondrial cristae ultrastructure, compared with controls. Thus, our data suggest that mutations in MIEF2 result in imbalanced mitochondrial dynamics and a combined respiratory chain enzyme defect in skeletal muscle, leading to mitochondrial myopathy

Testing in Mice the Hypothesis That Melanin Is Protective in Malaria Infections

Malaria has had the largest impact of any infectious disease on shaping the human genome, exerting enormous selective pressure on genes that improve survival in severe malaria infections. Modern humans originated in Africa and lost skin melanization as they migrated to temperate regions of the globe. Although it is well documented that loss of melanization improved cutaneous Vitamin D synthesis, melanin plays an evolutionary ancient role in insect immunity to malaria and in some instances melanin has been implicated to play an immunoregulatory role in vertebrates. Thus, we tested the hypothesis that melanization may be protective in malaria infections using mouse models. Congenic C57BL/6 mice that differed only in the gene encoding tyrosinase, a key enzyme in the synthesis of melanin, showed no difference in the clinical course of infection by Plasmodium yoelii 17XL, that causes severe anemia, Plasmodium berghei ANKA, that causes severe cerebral malaria or Plasmodium chabaudi AS that causes uncomplicated chronic disease. Moreover, neither genetic deficiencies in vitamin D synthesis nor vitamin D supplementation had an effect on survival in cerebral malaria. Taken together, these results indicate that neither melanin nor vitamin D production improve survival in severe malaria

Representation of gender in migrant health studies – a systematic review of the social epidemiological literature

Wandschneider L, Batram-Zantvoort S, Razum O, Miani Vial C. Representation of gender in migrant health studies – a systematic review of the social epidemiological literature. International Journal for Equity in Health. 2020;19: 181.Background Gender as a social construct contributes to determine who migrates and which migration-related risks and opportunities emerge in all phases of the migration trajectory. Simultaneously, migration influences the individual as well as societal definition and perception of gender roles. An explicit gender perspective in migration-related epidemiological research can contribute to adequately analyse and interpret the health of migrants. This systematic review gives a comprehensive overview on how gender has been conceptualised, operationalised and measured in social epidemiologic studies aiming to assess the influence of gender on health among migrants. Methods We searched PubMed, Embase, CINAHL, the Cochrane Library, EconLit and PsycINFO and conducted backward reference searching. Reviewers independently selected studies, extracted data and conducted the quality assessment. Eligible studies actively aimed to understand, identify or explain the influence of gender on migrants’ health, whereby the role of gender can encompass a variety of mechanisms, processes or states of differentiation, discrimination and/or inequality. Results Almost all of the 43 studies were cross-sectional and focussed on health outcomes in the post-migration phase. The most common theme of research was the health of male migrants in the US, and in particular of men who have sex with men (MSM). All studies treated gender as a binary variable (men vs. women), without discussing additional types of gender identities. A minority of studies differentiated clearly between sex and gender. Gender was mostly operationalised through attitudes toward gender roles and gender-based discrimination, experienced at the individual level. Community and societal level gender measures capturing structural gender determinants were underrepresented. Conclusions The intersections of migration and gender suggested synergistic effects on health that only become visible when considering those two social determinants together. Future research needs to embrace a multilevel and non-binary understanding of gender and reflect on the influence of gender in the different phases of the migration journey

Advanced DNA- and protein-based methods for the detection and investigation of food allergens

32 pages, 3 tables, 1 figureCurrently, food allergies are an important health concern worldwide. The presence of undeclared allergenic ingredients or the presence of traces of allergens due to contamination during food processing poses a great health risk to sensitized individuals. Therefore, reliable analytical methods are required to detect and identify allergenic ingredients in food products. The present review addresses the recent developments regarding the application of DNA- and protein-based methods for the detection of allergenic ingredients in foods. The fitness-for-purpose of reviewed methodology will be discussed, and future trends will be highlighted. Special attention will be given to the evaluation of the potential of newly developed and promising technologies that can improve the detection and identification of allergenic ingredients in foods, such as the use of biosensors and/or nanomaterials to improve detection limits, specificity, ease of use, or to reduce the time of analysis. Such rapid food allergen test methods are required to facilitate the reliable detection of allergenic ingredients by control laboratories, to give the food industry the means to easily determine whether its product has been subjected to cross-contamination and, simultaneously, to identify how and when this cross-contamination occurred.Peer reviewe

Zuckerman on Australian Civil Procedure

Zuckerman on Australian Civil Procedure is an important new text that provides a rigorous, principles-based analysis of civil procedure in Australia. Civil procedure lies at the heart of the judicial process. Relevant principles are explored against a backdrop of State, Territory and Federal rules of procedure, and solutions are offered to difficult issues encountered in practice and to unsettled questions of law

Linear Mesostructures in DNA–Nanorod Self-Assembly

The assembly of molecules and nanoscale objects into one-dimensional (1D) structures, such as fibers, tubules, and ribbons, typically results from anisotropic interactions of the constituents. Conversely, we found that a 1D structure can emerge <i>via</i> a very different mechanism, viz, the spontaneous symmetry breaking of underlying interparticle interactions during structure formation. For systems containing DNA-decorated nanoscale rods, this mechanism, driven by flexible DNA chains, results in the formation of 1D ladderlike mesoscale ribbons with a side-by-side rod arrangement. Detailed structural studies using electron microscopy and <i>in situ</i> small-angle X-ray scattering (SAXS), as well as analysis of assembly kinetics, reveal the role of collective DNA interactions in the formation of the linear structures. Moreover, the reversibility of DNA binding facilitates the development of hierarchical assemblies with time. We also observed similar linear structures of alternating rods and spheres, which implies that the discovered mechanism is generic for nanoscale objects interacting <i>via</i> flexible multiple linkers

Novel alginate-based nanocarriers as a strategy to include high concentrations of hydrophobic compounds in hydrogels for topical application

International audienceThe cutaneous penetration of hydrophobic active molecules is of foremost concern in the dermatology and cosmetic formulation fields. The poor solubility in water of those molecules limits their use in hydrophilic forms such as gels, which are favored by patients with chronic skin disease. The aim of this work is to design a novel nanocarrier of hydrophobic active molecules and to determine its potential as an ingredient of a topical form. The nanocarrier consists of an oily core surrounded by a protective shell of alginate, a natural polysaccharide isolated from brown algae. These calcium alginate-based nanocarriers (CaANCs) were prepared at room temperature and without the use of organic solvent by an accelerated nanoemulsification-polymer crosslinking method. The size (hydrodynamic diameter ~200 nm) and surface charge (zeta potential ~ − 30 mV) of the CaANCs are both compatible with their application on skin. CaANCs loaded with a fluorescent label were stable in model hydrophilic galenic forms under different storage conditions. Curcumin was encapsulated in CaANCs with an efficiency of ~95%, fully retaining its antioxidant activity. The application of the curcumin-loaded CaANCs on excised human skin led to a significant accumulation of the active molecules in the upper layers of the skin, asserting the potential of these nanocarriers in active pharmaceutical and cosmetic ingredients topical delivery