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Engineering Organoids for Modeling PKU

Engineering Organoids for Modeling PKU | iBB | Scoop.it

Phenylketonuria (PKU) is a recessive genetic disorder of amino-acid metabolism, where impaired phenylalanine hydroxylase function in the liver of patients leads to the accumulation of neurotoxic phenylalanine levels in the brain. Despite the current knowledge, the chronic effect of PKU in the brain is still poorly understood. In a recent publication in Frontiers in Molecular Neurosciences, DBE faculty and SCERG-iBB researcher Tiago Fernandes, discusses the need for better predictive models, able to recapitulate specific mechanisms of this disease. New exciting in vitro platforms to model specific PKU-derived neuronal impairment are presented in a attempt to understand the impact of phenylalanine in the brain of patients, and ultimately contribute to the understanding of this disease.

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Development of 3D High-Quality PDMS Microfluidic Chips Based on Micromilling Technology

Development of 3D High-Quality PDMS Microfluidic Chips Based on Micromilling Technology | iBB | Scoop.it

In recent years, there has been an increased interest in exploring the potential of micro-and mesoscale milling technologies for developing cost-effective microfluidic systems with high design flexibility and a rapid microfabrication process that does not require a cleanroom. Nevertheless, the number of current studies aiming to fully understand and establish the benefits of this technique in developing high-quality microsystems with simple integrability is still limited. In a recent paper published in Micromachines, BERG-iBB researches, Ana Azevedo and Amin Javidanbardan, in collaboration, with João Pedro Conde and Virginia Chu from INESC-MN, describe a systematic methodology for developing 3D high-quality thermoplastic-based molds for microfluidic structures based on micromilling technology. The work was performed under the Marie Skłodowska-Curie grant agreement No. 812909 CODOBIO, within the Marie Skłodowska-Curie European Training Networks framework.

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A Neofunctionalized Transcription Factor Controls Azole Resistance in C. glabrata

A Neofunctionalized Transcription Factor Controls Azole Resistance in C. glabrata | iBB | Scoop.it

The prevalence of antifungal resistance in Candida glabrata, especially against azole drugs, results in difficult-to-treat and potentially life-threatening infections. In this study, the role of a newly described transcription factor, Mar1, in azole susceptibility was explored. Using RNA-sequencing, its role in the transcriptome-wide response to fluconazole is assessed, leading to the elucidation of its role in modulating azole susceptibility, dependent on membrane sphingolipid incorporation, membrane permeability, and intracellular drug accumulation. Altogether, a regulatory pathway modulating azole susceptibility in C. glabrata is proposed, resulting from what appears to be a neofunctionalization of a Hap1-like transcription factor. These results obtained by an international team led by Miguel Cacho Teixeira, BSRG-iBB, just published in Journal of Fungi, are expected to contribute to maintain the usability of this drug in antifungal therapy.

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Engineering Organoids for Modeling PKU

Engineering Organoids for Modeling PKU | iBB | Scoop.it

Phenylketonuria (PKU) is a recessive genetic disorder of amino-acid metabolism, where impaired phenylalanine hydroxylase function in the liver of patients leads to the accumulation of neurotoxic phenylalanine levels in the brain. Despite the current knowledge, the chronic effect of PKU in the brain is still poorly understood. In a recent publication in Frontiers in Molecular Neurosciences, DBE faculty and SCERG-iBB researcher Tiago Fernandes, discusses the need for better predictive models, able to recapitulate specific mechanisms of this disease. New exciting in vitro platforms to model specific PKU-derived neuronal impairment are presented in a attempt to understand the impact of phenylalanine in the brain of patients, and ultimately contribute to the understanding of this disease.

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Metabolic Engineering of Saccharomyces cerevisiae Towards the Valorization of Pectin-rich Residues

Metabolic Engineering of Saccharomyces cerevisiae Towards the Valorization of Pectin-rich Residues | iBB | Scoop.it

A recent article published in the journal Metabolic Engineering reports the metabolic engineering of the yeast Saccharomyces cerevisiae envisaging the fast and complete consumption of D-galacturonic acid (d-GalUA) in crude sugar beet pulp hydrolysate under aerobic conditions. To this end, the fungal d-GalUA pathway was inserted in an S cerevisiae strain equipped with an NAD-dependent glycerol catabolic pathway. The constructed strain was able to consume d-GalUA with the highest reported maximum specific rate in synthetic minimal medium when glycerol was added. This work is the result of joint research in the framework of project YEASTPEC (Engineering of the yeast Saccharomyces cerevisiae for bioconversion of pectin-containing agro-industrial side-streams), funded through the ERA-IB scheme. In Portugal, the project was led by Isabel Sá-Correia (BSRG/iBB), in Germany by Elke Nevoigt, Jacobs University (corresponding author) and Wolfgang Liebl, TUM, and at VTT, Finland, by Peter Richard. The BSRG/iBB PhD graduate in Biotechnology and Biosciences Luis Martins also co-authored this article.

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Algae2Fish Project Featured in PT Newspaper Público

Algae2Fish Project Featured in PT Newspaper Público | iBB | Scoop.it

"This week in the Portuguese newspaper "Público" you will find a summary of the Algae2Fish project, where you can read about the reasons behind the project and its perspectives for the next two years. The team, composed by professor Frederico Ferreira, Dr. Paola Sanjuan Alberte, Dr. Carlos Rodrigues, and Msc Diana Marques, with the support of The Good Food Institute, is currently working to produce the first cell-cultured sea bass fillet!"

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Special Issue: Coral Reef Ecology, Conservation, and Inspiration for Marine Drugs Development

Special Issue: Coral Reef Ecology, Conservation, and Inspiration for Marine Drugs Development | iBB | Scoop.it

Marine invertebrates together with a plethora of symbiotic and free-living algae, fungi and prokaryotes are amidst the most prolific producers of bioactive compounds in coral reefs and marine environments at large. Their natural products often show astounding structural novelty and complexity, facilitating chemically mediated behaviours and interspecies interactions from competition to cooperation. There is great potential for a minimally invasive and economically reliable exploitation of bioactive secondary metabolites from the highly diverse and chemically complex reef communities. iBB researchers Tina Keller-Costa and Rodrigo Costa (BSRG) are guest editing a special issue on Coral Reef Ecology, Conservation and Inspiration for Marine Drugs Development in the Journal Marine Drugs and cordially invite the scientific community to contribute original research or review articles on the role of natural products in coral reef ecology and conservation, organismal interactions and biotechnology.

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Seabass Fillets from 3D-Printed Cells

Seabass Fillets from 3D-Printed Cells | iBB | Scoop.it

The project Algae2Fish led by Frederico Ferreira from SCERG-iBB has received funding from the Global Food Institute with the aim of developing a boneless cultivated seabass fillet. 3D printing technology will be used to produce scaffolds that will give the fillet structure, replicating the fibrous texture of fish. The scaffolds will be formed using material from algae and plants, with the algae contributing valuable omega-3 fatty acids such as those found in conventional fish. Read more about the project here.

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Today’s Pharma and Biotech Projects: A Phased Approach

Today’s Pharma and Biotech Projects: A Phased Approach | iBB | Scoop.it

The general outline of a pharma or biotech engineering project includes phases and tasks that typically span 2–3 years. The concept of phased engineering, procurement, and construction (EPC) is revisited in a paper co-authored by José Cardoso Menezes from BERG-iBB and colleagues and published in Pharmaceutical Engineering. The concept is further updated with risk-based considerations specifically regarding the commissioning, qualification, and validation (CQV) of general life-cycle principles for pharma and biotech projects.

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Acyl-chain Saturation Regulates the Order of Phosphatidylinositol 4,5-bisphosphate Nanodomains

Acyl-chain Saturation Regulates the Order of Phosphatidylinositol 4,5-bisphosphate Nanodomains | iBB | Scoop.it

PI(4,5)P2 is a phospholipid found mostly in the plasma membrane of eukaryotic cells, where it plays a crucial role in processes like vesicle trafficking, cytoskeletal regulation, ion channel function, viral assembly and budding. While most phospholipids show considerable acyl-chain diversity, PI(4,5)P2 lipids are exceptionally enriched in specific acyl-chains, the most frequent composition in mammalian cells being 1-stearoyl-2-arachidonyl (18:0 20:4). The biological functions that call for this specific enrichment are still not fully clear. In a recent paper published in Communications Chemistry, a BSIRG-iBB team led by Fábio Fernandes together with the teams of Dr. Nuno Santos (IMM) and Dr. Manuel Melo (ITQB) identified a previously unreported increase in membrane order upon calcium-dependent PI(4,5)P2 clustering. Remarkably, the interaction of saturated PI(4,5)P2 with calcium culminated in the formation of gel nanodomains for fully saturated PI(4,5)P2, and the formation of these gel domains was abrogated in the presence of 18:0 20:4 polyunsaturated PI(4,5)P2. These results support a role of (18:0 20:4)PI(4,5)P2 in inhibiting the formation of highly ordered PI(4,5)P2 nanodomains in the plasma membrane.

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Quantitative FRET Microscopy Reveals a Crucial Role of Cytoskeleton in Promoting PI(4,5)P2 Confinement

Quantitative FRET Microscopy Reveals a Crucial Role of Cytoskeleton in Promoting PI(4,5)P2 Confinement | iBB | Scoop.it

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is crucial to many cellular processes in eukaryotes, including membrane trafficking, signal transduction, ion channel function  and cytoskeleton dynamics. This function multiplicity is partially achieved through a dynamic spatiotemporal organization of PI(4,5)P2 within the membrane. In a recent paper published in IJMS, an IBB team (Maria J. Sarmento, Luís Borges-Araújo, Sandra N.Pinto, Nuno Bernardes, Joana Ricardo, Ana Coutinho, Manuel Prieto and Fábio Fernandes) was able to quantify PI(4,5)P2 confinement in living cells making use of FRET imaging measurements. PI(4,5)P2 was found to be significantly compartmentalized at the plasma membrane of HeLa cells. These PI(4,5)P2 enriched domains were shown to not depend on cholesterol content, ruling out an association with lipid rafts. On the other hand, upon inhibition of actin polymerization, compartmentalization of PI(4,5)P2 was almost entirely eliminated, confirming that the cytoskeleton network is the critical component responsible for the formation of nanoscale PI(4,5)P2 domains.

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Application of Perinatal Derivatives in Animal Models on Cutaneous Wound Healing

Application of Perinatal Derivatives in Animal Models on Cutaneous Wound Healing | iBB | Scoop.it

Many studies that apply PnD in pre-clinical cutaneous wound healing models show large variations in the choice of the animal species (e.g., large animals, rodents), the choice of diabetic or non-diabetic animals, the type of injury (full-thickness wounds, burns, radiation-induced wounds, skin flaps), the source and type of PnD (placenta, umbilical cord, fetal membranes, cells, secretomes, tissue extracts), the method of administration (topical application, intradermal/subcutaneous injection, intravenous or intraperitoneal injection, subcutaneous implantation), and the type of delivery systems (e.g., hydrogels, synthetic or natural biomaterials as carriers for transplanted cells, extracts or secretomes). In a collaborative work coordinated by Prof. Pedro Fonte under the COST Action SPRINT (CA17116), the Postdoc researcher Ana Macedo and Master student Francisca Mendes from BERG-iBB, provided a comprehensive and integrative overview of the application of PnD in wound healing to assess its efficacy in preclinical animal models. The review was published in Frontiers in Bioengineering and Biotechnology.

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Miguel Fuzeta to Defend PhD Thesis in Bioengineering

Miguel Fuzeta to Defend PhD Thesis in Bioengineering | iBB | Scoop.it

 Miguel de Almeida Fuzeta will be defending his PhD thesis in Bioengineering on Wednesday the 27th october 2021 at 10:00 h (https://videoconf-colibri.zoom.us/j/81143862412). During the last years, and under the supervision of Cláudia Lobato Silva from SCERG and BERG-IBB and Diana Maria Diez Gaspar from FEUP, Miguel focused his efforts on the development of Bioprocesses for the scalable manufacturing of extracellular vesicles derived from mesenchymal stromal cells. The title of the thesis is “Scalable Production of Extracellular Vesicles Derived from Mesenchymal Stromal Cells for Cancer-Targeted Drug Delivery”.

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The Azurin-Derived Peptide CT-p19LC Exhibits Membrane-Active Properties and Induces Cancer Cell Death

The Azurin-Derived Peptide CT-p19LC Exhibits Membrane-Active Properties and Induces Cancer Cell Death | iBB | Scoop.it

The bacterial protein azurin shows an unexpected therapeutic effect against various types of cancer. This property seems to result from its unique structural and surface features. A 28-residue peptide (named p28) derived from the middle part of azurin has been subjected to various studies and reached two clinical trials phase I in US. In a recent paper published in Biomedicines, a iBB team (Ana Rita Garizo, Lígia Coelho, Sandra Pinto, Tiago Dias, Fábio Fernandes, Nuno Bernardes and Arsénio M Fialho) were able to identified another anticancer bioactive peptide (CT-p19LC) derived from the C-terminal of azurin. CT-p19LC proved to interact preferentially with cancer cells, causing a significative inhibition of cell proliferation in a dose dependent manner. Moreover, it is proposed that the mode of action of CT-p19LC involves perturbation or disruption of cancer cell membranes. Overall this study highlights the relevance of azurin as a source of bioactive peptides with potential application in cancer therapies.

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Microchromatography Integrated with Impedance Sensor for Bioprocess Optimization

Microchromatography Integrated with Impedance Sensor for Bioprocess Optimization | iBB | Scoop.it

The development of new scale-down models for accelerated and cost-effective biopharmaceutical process development has been receiving considerable attention in the last decade. Microfluidic systems have emerged as a particularly attractive candidate by offering miniaturization, parallelization, and allowing continuous and precise pumping and online monitoring possible. In a collaborative work, published in Journal of Chromatography A, BERG-iBB researchers Ana Azevedo and Amin Javidanbardan, together with INESC-MN researchers João Pedro Conde and Virginia Chu, propose a simple and cost-effective method for developing microfluidic chromatographic systems with integrated sensors. Fabrication and integration of microsensors, in this case, an impedance sensor, in each microcolumn provided the possibility of parallelizing experiments with separate online monitoring. The work was performed under the Marie Skłodowska-Curie grant agreement No. 812909 CODOBIO, within the Marie Skłodowska-Curie European Training Networks framework.

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Integral Analysis of Liquid-Hot-Water Pretreatment of Wheat Straw

Integral Analysis of Liquid-Hot-Water Pretreatment of Wheat Straw | iBB | Scoop.it

Developing viable biorefineries is urgent to support the transition to a sustainable society. Lignocellulosic biomass is a crucial renewable feedstock, but usually a combination of pretreatments is necessary to extract both sugars and lignin. In a recent paper published in the journal Sustainability, the M.Sc. student Manuel Dias and Carla C.C.R. de Carvalho (BERG-iBB) collaborated with researchers from Technische Universität Wien (Vienna, Austria) under supervision of Prof Anton Friedl, to study liquid-hot-water (LHW) as pretreatment for hemicellulose hydrolysis. Assessment of different LHW conditions allowed the determination of those leading to high sugar concentration and low concentration of degradation products. The lignin remaining in the solid phase could be extracted and hydrolysed. By including the analysis of lignin hydrolysis into the standard sugar and degradation products in LHW, it was possible to make an integrated decision to valorize the different lignocellulosic components of wheat straw.

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Exploring the Biological Function of Efflux Pumps for the Development of Superior Industrial Yeasts

Exploring the Biological Function of Efflux Pumps for the Development of Superior Industrial Yeasts | iBB | Scoop.it

The economic competitiveness of yeast-mediated bioprocesses in Chemical Biotechnology requires high tolerance of industrial strains to the multiple stresses that occur. Among the mechanisms used by yeast to overcome those deleterious effects is the activity of plasma membrane transporters involved in multidrug/multixenobiotic resistance (MDR/MXR). A new review article on these still poorly characterized transporters belonging to the MFS and the ABC Superfamily in yeasts of biotechnological relevance has just been published. The reported role of specific transporters in increasing the secretion of metabolites and other added-value bioproducts is also highlighted. The review article is co-authored by the BSRG-iBB researchers Isabel Sá-Correia and Cláudia P. Godinho and was published in the journal Current Opinion in Biotechnology (special Issue: Chemical Biotechnology 2022).

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Project YumAlgae

Project YumAlgae | iBB | Scoop.it

Consumer acceptance of microalgae products is often hampered by their colour, “fishy” smell and flavor. An international project with research teams from ISA (PI Prof. Anabela Raymundo), IST (Carla de Carvalho, iBB-BERG), Norce (Norway) and the company Pagarete Microalgae solutions (Portugal) is aimed at the use of enzymes to improve the overall sensory quality of microalgal ingredients. The project, entitled “YUM ALGAE - enzYmes for improved sensory qUality of MicroALGAE ingredients in foods”, is funded in ca. 1 million euros by the Iceland, Liechtenstein, Norway grants (EEA grants, Blue Growth programme).

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Ana Melo Delivers Invited Seminar at the Portuguese Neuroscience Meeting

Ana Melo Delivers Invited Seminar at the Portuguese Neuroscience Meeting | iBB | Scoop.it

Ana Melo gave an invited talk during the XVII Meeting of the Portuguese Society for Neuroscience, at Coimbra, 1 - 3 December, 2021. She presented recent work focused on characterizing the distinct conformational dynamics of the flanking polyQ regions in the membrane-bound state of Huntington exon 1, and its role in Huntington´s disease. Her presentation was in the framework of the SPB Symposium: “A biophysical perspective on degenerative diseases: protein assembly and phase separation”, together with Sandra Macedo Ribeiro (IBMC- i3S) and Salvador Ventura (IBB-Universitat Autonoma de Barcelona).

 

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Implementation of Synthetic Pathways towards Microbe-Based Production of Non-Natural Carboxylic Acids

Implementation of Synthetic Pathways towards Microbe-Based Production of Non-Natural Carboxylic Acids | iBB | Scoop.it

Carboxylic acids (CAs) are considered key players in the implementation of more sustainable industrial processes due to their potential to replace a set of oil-derived commodity chemicals and there is growing interest in producing them through microbial processes. While many CAs are intermediates of microbial central carbon metabolism, and therefore envisaging their production in a host of choice is relatively straightforward; for other CAs this approach is difficult. This could be because they do not occur naturally (as is the case for levulinic acid) or because the described production pathway cannot be easily ported (as it is the case for adipic, muconic or glucaric acids). In a review published in Journal of Fungi, Nuno Mira’s team (iBB) reviewed the synthetic biology approaches that have been made towards enabling the production of non-natural CAs in microbes, with a large emphasis on metabolic retrobiosynthesis methodologies. Additionally, the authors also reviewed the pathway prospecting studies towards microbial levulinic, poly-lactic and methacrylic acid production, as two case-studies where there is a need to bridge the gap between natural CAs and their non-natural industrial derivatives.

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Special Issue "Bioprocess Engineering: Sustainable Manufacturing for a Green Society"

Special Issue "Bioprocess Engineering: Sustainable Manufacturing for a Green Society" | iBB | Scoop.it

The mild operational conditions typically required by biobased production processes, together with the selective nature of biocatalysts, microbial diversity and tunability, and the century-long record of fermentation, clearly place bioprocesses as the primary contenders, by far, in achieving the generalized implementation of efficient, green manufacturing strategies. Moreover, by overlapping with the biorefinery approach, the foundations needed for bioprocesses to embrace the circular economy concept are set. In this Special Issue on “Bioprocess Engineering: Sustainable Manufacturing for a Green Society", guest edited by Pedro Fernandes and Carla de Carvalho (iBB-BERG) in Processes, the papers will discuss new bioproducts and concomitant bioengineering approaches to achieve a sustainable and environmentally friendly economy.

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Matilde Marques Wins Poster Prize at MICROBIOTEC21

Matilde Marques Wins Poster Prize at MICROBIOTEC21 | iBB | Scoop.it

PhD student Matilde Marques from DBE and iBB-BSRG received a Best Poster Prize for her video-poster presented at the Microbiotec21 web-conference. Matilde showed her work on metagenomics of viral communities in healthy and diseased octocorals. Matilde is a first year PhD student of the MIT Portugal program supervised by Rodrigo Costa and Tina Keller-Costa from IST and Raquel Peixoto from KAUST. Her thesis project focuses on developing microbiome therapy strategies to improve octocoral health. Congrats, Matilde!

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Magnetic Particles for the Purification of DNA Scaffolds for Biomanufacturing DNA-Origami Nanostructures

Magnetic Particles for the Purification of DNA Scaffolds for Biomanufacturing DNA-Origami Nanostructures | iBB | Scoop.it

Asymmetric PCR (aPCR) is often used to generate single-stranded DNA (ssDNA) scaffolds, which can then be assembled into nanoobjects by the DNA-origami technique. The scaffolds are usually purified by agarose gel extraction, a laborious, time consuming, limited, and non-scalable technique that presents low recovery yields, delivers low-quality products. To overcome such pitfalls, Ana Silva-Santos, Rui Silva, Sara Rosa and Miguel Prazeres from BERG-iBB, in collaboration with Pedro Paulo from CQE developed a simple, fast, and potentially scalable affinity-based method comprising magnetic particles. Specifically, scaffolds were synthesized by aPCR and purifed using magnetic particles functionalized with a 20 nt oligonucleotide complementary to the 3′ end of the target. The purified scaffolds were used to assemble 31 and 63 bp edge length tetrahedra with short oligonucleotides and thermal annealing, demonstrating the potential of affinity-based magnetic beads in the production of DNA-origami nanostructures. The work was published in ACS Applied Nanomaterials.

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Opportunities in Continuous Manufacturing of Large Molecules

Opportunities in Continuous Manufacturing of Large Molecules | iBB | Scoop.it

Continuous manufacturing has attracted significant interest over the past decade for small molecules formulated as drug products. The case for adopting continuous manufacturing platforms for manufacturing biologics (i.e., large proteins or biologic products such as vaccines) is made in a paper co-authored by José Cardoso Menezes from BERG-iBB and colleagues and published in Pharmaceutical Engineering. The article briefly reviews continuous biomanufacturing (CBM) at a time of very high and global demand for vaccines as well as increased demand for cell and gene therapy products.

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Antitumour and Antiproliferative Effect of Xanthohumol-loaded PLGA Nanoparticles on Melanoma

Antitumour and Antiproliferative Effect of Xanthohumol-loaded PLGA Nanoparticles on Melanoma | iBB | Scoop.it

Cutaneous melanoma is the deadliest type of skin cancer and current treatment is still inadequate, with low patient survival rates. The use of polyphenols loaded into nanoparticles could potentially address the lack of efficacy of current therapy. In a collaborative work published in a special issue of the journal Materials, with researchers from the University of Porto, Pedro Fonte and Ana Macedo from BERG-iBB assessed the potential of xanthohumol-loaded nanoparticles to treat melanoma. Nanoparticles had a size of about 300 nm and a PdI of 0.259, while achieving a xanthohumol loading of about 90%. The viability study showed similar cytoxicity between the xanthohumol and xanthohumol-loaded nanoparticles at 48 h with the IC50 established at 10 µM.  The ultimate anti-melanoma effect emerged from an association between the viability, migration and macrophagic phenotype modulation. These results display the remarkable antitumour effect of the xanthohumol-loaded nanoparticles and are the first advance towards the application of a nanoformulation to deliver xanthohumol to reduce adverse effects by currently employed chemotherapeutics.

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Lipid Changes in Daptomycin-resistant MRSA During Antibiotic Exposure

Lipid Changes in Daptomycin-resistant MRSA During Antibiotic Exposure | iBB | Scoop.it

The cyclic anionic lipopeptide daptomycin (DAP) is used in the treatment of severe infections caused by Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). DAP resistance, though rare, often results in treatment failure. Paradoxically, in MRSA, DAP resistance is usually accompanied by a concomitant decrease in b-lactam resistance in what is known as the ‘see-saw effect’. In a recent publication in the Journal of Antimicrobial Chemotherapy, Carla CCR de Carvalho (iBB-BERG), Agustina Taglialegna and Adriana E. Rosato (currently at Riverside University Health System, USA), showed that the post-translocational protein PrsA has a major role in orchestrating the cell membrane lipid adaptation associated with the see-saw effect, in addition to its function required for the posttranscriptional maturation of PBP 2a. This study contributes greatly to the understanding of MRSA biology and of the impact of DAP/b-lactam on the cell membrane/cell wall machinery.

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