Publications by authors named "Joana Silva"

420 Publications

Glucocorticoid receptor triggers a reversible drug-tolerant dormancy state with acquired therapeutic vulnerabilities in lung cancer.

Nat Commun 2021 07 16;12(1):4360. Epub 2021 Jul 16.

Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

The glucocorticoid receptor (GR) regulates gene expression, governing aspects of homeostasis, but is also involved in cancer. Pharmacological GR activation is frequently used to alleviate therapy-related side-effects. While prior studies have shown GR activation might also have anti-proliferative action on tumours, the underpinnings of glucocorticoid action and its direct effectors in non-lymphoid solid cancers remain elusive. Here, we study the mechanisms of glucocorticoid response, focusing on lung cancer. We show that GR activation induces reversible cancer cell dormancy characterised by anticancer drug tolerance, and activation of growth factor survival signalling accompanied by vulnerability to inhibitors. GR-induced dormancy is dependent on a single GR-target gene, CDKN1C, regulated through chromatin looping of a GR-occupied upstream distal enhancer in a SWI/SNF-dependent fashion. These insights illustrate the importance of GR signalling in non-lymphoid solid cancer biology, particularly in lung cancer, and warrant caution for use of glucocorticoids in treatment of anticancer therapy related side-effects.
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http://dx.doi.org/10.1038/s41467-021-24537-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285479PMC
July 2021

Microalgae as Sustainable Bio-Factories of Healthy Lipids: Evaluating Fatty Acid Content and Antioxidant Activity.

Mar Drugs 2021 Jun 23;19(7). Epub 2021 Jun 23.

Mass Spectrometry Centre, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Santiago University Campus, 3810-193 Aveiro, Portugal.

The demand for sustainable and environmentally friendly food sources and food ingredients is increasing, and microalgae are promoted as a sustainable source of essential and bioactive lipids, with high levels of omega-3 fatty acids (ω-3 FA), comparable to those of fish. However, most FA screening studies on algae are scattered or use different methodologies, preventing a true comparison of its content between microalgae. In this work, we used gas-chromatography mass-spectrometry (GC-MS) to characterize the FA profile of seven different commercial microalgae with biotechnological applications (, sp., and ). Screening for antioxidant activity was also performed to understand the relationship between FA profile and bioactivity. Microalgae exhibited specific FA profiles with a different composition, namely in the ω-3 FA profile, but with species of the same phylum showing similar tendencies. The different lipid extracts showed similar antioxidant activities, but with a low activity of the extracts of . Overall, this study provides a direct comparison of FA profiles between microalgae species, supporting the role of these species as alternative, sustainable, and healthy sources of essential lipids.
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http://dx.doi.org/10.3390/md19070357DOI Listing
June 2021

Integration of population and functional genomics to understand mechanisms of artemisinin resistance in Plasmodium falciparum.

Int J Parasitol Drugs Drug Resist 2021 May 26;16:119-128. Epub 2021 May 26.

Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address:

Resistance to antimalarial drugs, and in particular to the artemisinin derivatives and their partner drugs, threatens recent progress toward regional malaria elimination and eventual global malaria eradication. Population-level studies utilizing whole-genome sequencing approaches have facilitated the identification of regions of the parasite genome associated with both clinical and in vitro drug-resistance phenotypes. However, the biological relevance of genes identified in these analyses and the establishment of a causal relationship between genotype and phenotype requires functional characterization. Here we examined data from population genomic and transcriptomic studies in the context of data generated from recent functional studies, using a new population genetic approach designed to identify potential favored mutations within the region of a selective sweep (iSAFE). We identified several genes functioning in pathways now known to be associated with artemisinin resistance that were supported in early population genomic studies, as well as potential new drug targets/pathways for further validation and consideration for treatment of artemisinin-resistant Plasmodium falciparum. In addition, we establish the utility of iSAFE in identifying positively-selected mutations in population genomic studies, potentially accelerating the time to functional validation of candidate genes.
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http://dx.doi.org/10.1016/j.ijpddr.2021.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187163PMC
May 2021

Early Life Antibiotics Influence In Vivo and In Vitro Mouse Intestinal Epithelium Maturation and Functioning.

Cell Mol Gastroenterol Hepatol 2021 Jun 6. Epub 2021 Jun 6.

Department of Pediatrics, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Danone Nutricia Research, Utrecht, the Netherlands.

Background & Aims: The use of antibiotics (ABs) is a common practice during the first months of life. ABs can perturb the intestinal microbiota, indirectly influencing the intestinal epithelial cells (IECs), but also directly can affect IECs independent of the microbiota. Previous studies have focused mostly on the impact of AB treatment during adulthood. However, the difference between the adult and neonatal intestine warrants careful investigation of AB effects in early life.

Methods: Neonatal mice were treated with a combination of amoxicillin, vancomycin, and metronidazole from postnatal day 10 to 20. Intestinal permeability and whole-intestine gene and protein expression were analyzed. IECs were sorted by a fluorescence-activated cell sorter and their genome-wide gene expression was analyzed. Mouse fetal intestinal organoids were treated with the same AB combination and their gene and protein expression and metabolic capacity were determined.

Results: We found that in vivo treatment of neonatal mice led to decreased intestinal permeability and a reduced number of specialized vacuolated cells, characteristic of the neonatal period and necessary for absorption of milk macromolecules. In addition, the expression of genes typically present in the neonatal intestinal epithelium was lower, whereas the adult gene expression signature was higher. Moreover, we found altered epithelial defense and transepithelial-sensing capacity. In vitro treatment of intestinal fetal organoids with AB showed that part of the consequences observed in vivo is a result of the direct action of the ABs on IECs. Lastly, ABs reduced the metabolic capacity of intestinal fetal organoids.

Conclusions: Our results show that early life AB treatment induces direct and indirect effects on IECs, influencing their maturation and functioning.
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http://dx.doi.org/10.1016/j.jcmgh.2021.05.019DOI Listing
June 2021

Year-round element quantification of a wide-ranging seabird and their relationships with oxidative stress, trophic ecology, and foraging patterns.

Environ Pollut 2021 Sep 2;284:117502. Epub 2021 Jun 2.

University of Coimbra, MARE - Marine and Environmental Sciences Centre, Department of Life Sciences, Calçada Martim de Freitas, 3000-456, Coimbra, Portugal. Electronic address:

Multidisciplinary approaches are essential to diligently assess environmental health status of ecosystems. In this study, year-round chemical elements' exposure and impacts were assessed on the wide-ranging Cory's shearwater Calonectris borealis breeding in Berlenga Island, offshore Portugal, North Atlantic Ocean. The aim was to identify potential contamination and oxidative stress sources associated with trophic ecology, habitat and spatial use, and foraging patterns. A set of 20 chemical elements were quantified, along with oxidative stress biomarkers, stable isotope analyses, and GPS tracking data. Birds presented higher accumulation to some non-essential elements along the year (i.e. arsenic, As; cadmium, Cd; mercury, Hg; lead, Pb; and strontium, Sr), in which concentrations were similar or surpassed other procellariform seabird populations all over the world. No significant differences were found for any of the elements between different periods within the breeding season, with exception of Hg. However, a Principal Component Analysis taking into consideration a group of elements showed differences between pre-laying and chick-rearing periods, with overall higher concentrations in the former. Individuals spending more time engaging in an intensive search for food, and in more coastal environments, presented overall higher element concentrations, and particularly Hg. Contrary to expectations, no relationships were found between chemical elements and oxidative stress. On the other hand, spatial use and foraging patterns of Cory's shearwaters influenced their oxidative stress responses. Our results highlight the need for multidisciplinary approaches to deepen understanding of the large-scale vulnerability of bioindicators such as seabirds and, by extension, the overall environmental health of ecosystems in which they rely.
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http://dx.doi.org/10.1016/j.envpol.2021.117502DOI Listing
September 2021

Tuberculosis in the paediatric age group: a reflection on transmission.

An Pediatr (Engl Ed) 2021 Jun 25;94(6):403-411. Epub 2020 Dec 25.

Servicio de Pediatría, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal; Centro Ambulatorio de Tuberculosis, Vila Nova de Gaia, Portugal.

Introduction: Paediatric tuberculosis (TB) disease continues to be a challenge. Difficulties in its diagnosis and limited experience on its treatment in children are some of the reasons to consider the need for specialized paediatric TB centres and to prioritize children in tuberculosis control programmes, particularly in low-incidence countries. We describe the paediatric tuberculosis cases managed in a specialized paediatric outpatient TB centre.

Patients And Methods: We conducted a retrospective analysis of epidemiological and clinical data on TB cases in patients aged less than 18 years in the period ranging from January 2007 to June 2017.

Results: We identified 46 cases of TB. The median age of the patients was 5 years (IQR, 1.75-13.25). Thirty cases (65.2%) were identified through screening following exposure to TB. Thirty-six children (78%) presented with a median duration of symptoms during 2 weeks, the most frequent being cough (54%) and fever (48%). The findings of the chest radiograph were abnormal in 73.9% of patients, and a CT scan was performed in 82.2%, the findings of which contributed significantly to the decision to treat in 85.3%. Despite collection of different microbiological specimens, diagnostic confirmation was possible in only 12 cases (26.1%). The results of culture and/or nucleic acid amplification tests were positive in 33.3% of samples of sputum, 28.1% of bronchoalveolar lavage and 12.9% of gastric aspirates. The most frequent diagnosis was pulmonary TB (n=31), followed by pleuropulmonary TB (n=6), lymph node disease (n=3), uveitis (n=2), bone tuberculosis, disseminated TB, cerebellar tuberculoma and erythema nodosum (each n=1).

Conclusions: Tuberculosis in children is an epidemiological indicator of recent transmission of Mycobacterium tuberculosis in the community. Efforts must be made to collect microbiological specimens before initiating treatment whenever possible. Management by an experienced paediatrics team allows an accurate diagnosis even when microbiologic confirmation is not possible.
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http://dx.doi.org/10.1016/j.anpede.2020.12.002DOI Listing
June 2021

Whole-genome analysis of Malawian Plasmodium falciparum isolates identifies possible targets of allele-specific immunity to clinical malaria.

PLoS Genet 2021 May 25;17(5):e1009576. Epub 2021 May 25.

Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.

Individuals acquire immunity to clinical malaria after repeated Plasmodium falciparum infections. Immunity to disease is thought to reflect the acquisition of a repertoire of responses to multiple alleles in diverse parasite antigens. In previous studies, we identified polymorphic sites within individual antigens that are associated with parasite immune evasion by examining antigen allele dynamics in individuals followed longitudinally. Here we expand this approach by analyzing genome-wide polymorphisms using whole genome sequence data from 140 parasite isolates representing malaria cases from a longitudinal study in Malawi and identify 25 genes that encode possible targets of naturally acquired immunity that should be validated immunologically and further characterized for their potential as vaccine candidates.
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http://dx.doi.org/10.1371/journal.pgen.1009576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184011PMC
May 2021

Marine endophytic fungi associated with Halopteris scoparia (Linnaeus) Sauvageau as producers of bioactive secondary metabolites with potential dermocosmetic application.

PLoS One 2021 13;16(5):e0250954. Epub 2021 May 13.

BioISI-Biosystems and Integrative Sciences Institute, Faculty of Sciences of the University of Lisbon, Lisbon, Portugal.

Marine fungi and, particularly, endophytic species have been recognised as one of the most prolific sources of structurally new and diverse bioactive secondary metabolites with multiple biotechnological applications. Despite the increasing number of bioprospecting studies, very few have already evaluated the cosmeceutical potential of marine fungal compounds. Thus, this study focused on a frequent seaweed in the Portuguese coast, Halopteris scoparia, to identify the endophytic marine fungi associated with this host, and assess their ability to biosynthesise secondary metabolites with antioxidative, enzymatic inhibitory (hyaluronidase, collagenase, elastase and tyrosinase), anti-inflammatory, photoprotective, and antimicrobial (Cutibacterium acnes, Staphylococcus epidermidis and Malassezia furfur) activities. The results revealed eight fungal taxa included in the Ascomycota, and in the most representative taxonomic classes in marine ecosystems (Eurotiomycetes, Sordariomycetes and Dothideomycetes). These fungi were reported for the first time in Portugal and in association with H. scoparia, as far as it is known. The screening analyses showed that most of these endophytic fungi were producers of compounds with relevant biological activities, though those biosynthesised by Penicillium sect. Exilicaulis and Aspergillus chevalieri proved to be the most promising ones for being further exploited by dermocosmetic industry. The chemical analysis of the crude extract from an isolate of A. chevalieri revealed the presence of two bioactive compounds, echinulin and neoechinulin A, which might explain the high antioxidant and UV photoprotective capacities exhibited by the extract. These noteworthy results emphasised the importance of screening the secondary metabolites produced by these marine endophytic fungal strains for other potential bioactivities, and the relevance of investing more efforts in understanding the ecology of halo/osmotolerant fungi.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250954PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118457PMC
May 2021

A rare cecal subepithelial tumor in a Crohn´s Disease patient.

Autops Case Rep 2020 Dec 8;11:e2020211. Epub 2020 Dec 8.

Centro Hospitalar Universitário do Porto, Department of Gastroenterology, Porto, Portugal.

Appendiceal tumors comprise a variety of histologic types, including appendiceal mucinous neoplasms, which can be grouped as premalignant lesions, tumors of uncertain malignant potential, and malignant lesions. The appendiceal mucinous neoplasms are characterized by mucinous epithelial proliferation with extracellular mucin and pushing tumor margins, commonly an incidental finding during operative exploration. We report the case of a low-grade appendiceal mucinous neoplasm presenting as a subepithelial lesion in Crohn´s Disease patient. The diagnosis was not straightforward, and only surgical resection allowed an accurate diagnosis. Although Inflammatory Bowel Disease is a risk factor for the development of colorectal neoplasms, the absolute risk for appendiceal tumors is uncertain. The frequency of progression to malignancy remains to be determined.
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http://dx.doi.org/10.4322/acr.2020.211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087374PMC
December 2020

Prognostic Value of Charlson Comorbidity Index in Acute Embolic Lower Limb Ischaemia Patients.

Ann Vasc Surg 2021 May 2. Epub 2021 May 2.

Angiology and Vascular Surgery Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

Introduction: Charlson Comorbidity Index (CCI) is commonly used in outcome studies to adjust for patient comorbid conditions but has not been specifically validated for use in acute embolic lower limb ischaemia (AELLI).

Objectives: The aim of this study was to access whether a high CCI score unadjusted (CCIu) and adjusted (CCIa) by age relates to major amputation and mortality after a first episode of AELLI.

Methods: The last 100 patients presenting with the first event of AELLI submitted to embolectomy at our Vascular Surgery Department were retrospectively evaluated. Patient characteristics, pre- and post-operative period variables were collected and CCIu and CCIa calculated. Survival predictors were analyzed using Cox regression. The area under the curve of the receiver operating characteristic curves was calculated to validate and determine the discriminating ability of CCIu and CCIa in predicting amputation rate and 30-day mortality. Youden index was used to determine the critical value. Survival analysis was performed with Kaplan-Meier method and differences between survival curves were tested with Log-Rank test. A P value of <0.05 was considered statistically significant.

Results: The mean age was 80.03±10.776 years and the mean follow-up 19.28±7.929 months. Amputation rate was 16%, 30-day mortality 21% and long-term mortality 42%. Patients with CCIu≥3 compared with patients with CCIu<3 had higher amputation rate (37.5% vs. 1.7%; OR:35.400), 30-day mortality (47.5% vs. 3.3%; OR:35.400) and global mortality (P=0.00). Also, patients with CCIa≥6 compared with patients with CCIa<6 had higher amputation rate (34.1% vs. 1.8%; OR:28.488), 30-day mortality (47.7% vs. 0.0%) and global mortality (P=0.00). Multivariate analysis showed that both CCIu and CCIa were independent predictors of amputation rate and 30-day mortality.

Conclusion: CCIu and CCIa have proven to be good predictors of amputation rate and survival, thus being a valuable prognostic factor in patients presenting with the first event of AELLI.
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http://dx.doi.org/10.1016/j.avsg.2021.04.022DOI Listing
May 2021

High-Yield Production of Nano-Lateral Size Graphene Oxide by High-Power Ultrasonication.

Materials (Basel) 2021 Apr 12;14(8). Epub 2021 Apr 12.

LEPABE, Faculdade de Engenharia, Universidade do Porto, 4200-180 Porto, Portugal.

Nanographene oxide (GOn) constitutes a nanomaterial of high value in the biomedical field. However, large scale production of highly stable aqueous dispersions of GOn is yet to be achieved. In this work, we explored high-power ultrasonication as a method to reduce particle size of GO and characterized the impact of the process on the physicochemical properties of the material. GOn was obtained with lateral dimensions of 99 ± 43 nm and surface charge of -39.9 ± 2.2 mV. High-power ultrasonication enabled an improvement of stability features, particularly by resulting in a decrease of the average particle size, as well as zeta potential, in comparison to GO obtained by low-power exfoliation and centrifugation (287 ± 139 nm; -29.7 ± 1.2 mV). Remarkably, GOn aqueous dispersions were stable for up to 6 months of shelf-time, with a global process yield of 74%. This novel method enabled the production of large volumes of highly concentrated (7.5 mg mL) GOn aqueous dispersions. Chemical characterization of GOn allowed the identification of characteristic oxygen functional groups, supporting high-power ultrasonication as a fast, efficient, and productive process for reducing GO lateral size, while maintaining the material's chemical features.
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http://dx.doi.org/10.3390/ma14081916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069895PMC
April 2021

A selective p53 activator and anticancer agent to improve colorectal cancer therapy.

Cell Rep 2021 Apr;35(2):108982

LAQV/REQUIMTE, Laboratório de Microbiologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. Electronic address:

Impairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring WT-like function to mutant (mut)p53 in human cancer cells. MANIO directly binds to the WT/mutp53 DNA-binding domain, enhancing the protein thermal stability, DNA-binding ability, and transcriptional activity. The high efficacy of MANIO as an anticancer agent toward cancers harboring WT/mutp53 is further demonstrated in patient-derived cells and xenograft mouse models of colorectal cancer (CRC), with no signs of undesirable side effects. MANIO synergizes with conventional chemotherapeutic drugs, and in vitro and in vivo studies predict its adequate drug-likeness and pharmacokinetic properties for a clinical candidate. As a single agent or in combination, MANIO will advance anticancer-targeted therapy, particularly benefiting CRC patients harboring distinct p53 status.
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http://dx.doi.org/10.1016/j.celrep.2021.108982DOI Listing
April 2021

First-Principles Model to Evaluate Quantitatively the Long-Life Behavior of Cellulose Acetate Polymers.

ACS Omega 2021 Mar 17;6(12):8028-8037. Epub 2021 Mar 17.

CERENA, Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal.

A deep understanding of the degradation of cellulose diacetate (CDA) polymer is crucial in finding the appropriate long-term stability solution. This work presents an investigation of the reaction mechanism of hydrolysis using electronic density functional theory calculations with the B3LYP/6-31++G** level of theory to determine the energetics of the degradation reactions. This information was coupled with the transition-state theory to establish the kinetics of degradation for both the acid-catalyzed and noncatalyzed degradation pathways. In this model, the dependence on water concentration of the polymer as a function of pH and the evaporation of acetic acid from the polymer is explicitly accounted for. For the latter, the dependence of the concentration of acetic acid inside the films with the partial pressure on the surrounding environment was measured by sorption isotherms, where Henry's law constant was measured as a function of temperature. The accuracy of this approach was validated through comparison with experimental results of CDA-accelerated aging experiments. This model provides a step forward for the estimation of CDA degradation dependence on environmental conditions. From a broader perspective, this method can be translated to establish degradation models to predict the aging of other types of polymeric materials from first-principles calculations.
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http://dx.doi.org/10.1021/acsomega.0c05438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014918PMC
March 2021

Disclosing the potential of eleganolone for Parkinson's disease therapeutics: Neuroprotective and anti-inflammatory activities.

Pharmacol Res 2021 Jun 31;168:105589. Epub 2021 Mar 31.

MARE - Marine and Environmental Sciences Centre, ESTM, Polytechnic of Leiria, 2520-614 Peniche, Portugal. Electronic address:

The treatment of Parkinson´s disease (PD) has benefited from significant advances resulting from the increasing research efforts focused on new therapeutics. However, the current treatments for PD are mostly symptomatic, alleviating disease symptoms without reversing or retarding disease progression. Thus, it is critical to find new molecules that can result in more effective treatments. Within this framework, this study aims to evaluate the neuroprotective and anti-inflammatory effects of three compounds (eleganolone, eleganonal and fucosterol) isolated from the brown seaweed Bifurcaria bifurcata. In vitro neuroprotective effects were evaluated on a PD cellular model induced by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y human cells, while lipopolysaccharide (LPS) - stimulated RAW 264.7 macrophages were used to evaluate the anti-inflammatory potential. Additionally, the underlying mechanisms of action were also investigated. Compounds were isolated by preparative chromatographic methods and their structural elucidation attained by NMR spectroscopy. Among the tested compounds, eleganolone (0.1-1 µM; 24 h) reverted the neurotoxicity induced by 6-OHDA in about 20%. The neuroprotective effects were mediated by mitochondrial protection, reduction of oxidative stress, inflammation and apoptosis, and inhibition of NF-kB pathway. The results suggest that eleganolone may provide advantages in the treatment of neurodegenerative conditions and, therefore, should be considered for future preclinical studies.
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http://dx.doi.org/10.1016/j.phrs.2021.105589DOI Listing
June 2021

Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from .

Molecules 2021 Mar 4;26(5). Epub 2021 Mar 4.

MARE-Marine and Environmental Sciences Centre, ESTM, Politécnico de Leiria, 2520-614 Peniche, Portugal.

Marine natural products have exhibited uncommon chemical structures with relevant antitumor properties highlighting their potential to inspire the development of new anticancer agents. The goal of this work was to study the antitumor activities of the brominated diterpene sphaerodactylomelol, a rare example of the dactylomelane family. Cytotoxicity (10-100 µM; 24 h) was evaluated on tumor cells (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-ML-28) and the effects estimated by MTT assay. Hydrogen peroxide (HO) levels and apoptosis biomarkers (membrane translocation of phosphatidylserine, depolarization of mitochondrial membrane potential, Caspase-9 activity, and DNA condensation and/or fragmentation) were studied in the breast adenocarcinoma cellular model (MCF-7) and its genotoxicity on mouse fibroblasts (L929). Sphaerodactylomelol displayed an IC range between 33.04 and 89.41 µM without selective activity for a specific tumor tissue. The cells' viability decrease was accompanied by an increase on HO production, a depolarization of mitochondrial membrane potential and an increase of Caspase-9 activity and DNA fragmentation. However, the DNA damage studies in L929 non-malignant cell line suggested that this compound is not genotoxic for normal fibroblasts. Overall, the results suggest that the cytotoxicity of sphaerodactylomelol seems to be mediated by an increase of HO levels and downstream apoptosis.
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http://dx.doi.org/10.3390/molecules26051374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961984PMC
March 2021

Ribo-ODDR: Oligo design pipeline for experiment-specific rRNA depletion in ribo-seq.

Bioinformatics 2021 Mar 15. Epub 2021 Mar 15.

Division of Oncogenomics, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, CX, 1066, The Netherlands.

Motivation: Ribosome Profiling (Ribo-seq) has revolutionized the study of RNA translation by providing information on ribosome positions across all translated RNAs with nucleotide-resolution. Yet several technical limitations restrict the sequencing depth of such experiments, the most common of which is the overabundance of rRNA fragments. Various strategies can be employed to tackle this issue, including the use of commercial rRNA depletion kits. However, as they are designed for more standardized RNAseq experiments, they may perform suboptimally in Ribo-seq. In order to overcome this, it is possible to use custom biotinylated oligos complementary to the most abundant rRNA fragments, however currently no computational framework exists to aid the design of optimal oligos.

Results: Here, we first show that a major confounding issue is that the rRNA fragments generated via Ribo-seq vary significantly with differing experimental conditions, suggesting that a "one-size-fits-all" approach may be inefficient. Therefore we developed Ribo-ODDR, an oligo design pipeline integrated with a user-friendly interface that assists in oligo selection for efficient experiment-specific rRNA depletion. Ribo-ODDR uses preliminary data to identify the most abundant rRNA fragments, and calculates the rRNA depletion efficiency of potential oligos. We experimentally show that Ribo-ODDR designed oligos outperform commercially available kits and lead to a significant increase in rRNA depletion in Ribo-seq.

Availability: Ribo-ODDR is freely accessible at https://github.com/fallerlab/Ribo-ODDR.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab171DOI Listing
March 2021

Literacy on tuberculosis in paediatric population and their caregivers. The importance of an outpatient tuberculosis centre.

Pulmonology 2021 Mar 5. Epub 2021 Mar 5.

Department of Pediatrics, Centro Hospitalar de Vila Nova de Gaia Espinho EPE Vila Nova de Gaia, Vila Nova de Gaia, Portugal.

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http://dx.doi.org/10.1016/j.pulmoe.2021.01.003DOI Listing
March 2021

Surgical Management of Odontogenic Infection in Sturge-Weber Syndrome: Report of a Case.

J Craniofac Surg 2021 Mar 4. Epub 2021 Mar 4.

Post-graduate student, Department of Oral and Maxillofacial Surgery, School of Dentistry, Universidade de Pernambuco (FOP/UPE) Oral and Maxillofacial Surgery (HUOC/FOP/UPE). University of Pernambuco Oral and Maxillofacial Surgery, Hospital de Emergência e Trauma Dom Luiz Gonzaga Fernandes Faculty of Dentistry of Pernambuco Oral and Maxillofacial Surgery (HR/FOP/UPE). University of Pernambuco Maxillofacial Surgery and Traumatology Service of Hospital da Restauração Oral and Maxillofacial Surgery, University of Pernambuco. Head of the Hospital da Restauração. Pernambuco, Brazil.

Abstract: Surgical management of odontogenic infections in Sturge-Weber Syndrome is challenging, due to the risk of massive bleeding and difficulty to achieve hemostasis. The authors describe the use of preoperative vascular embolization for oral surgery in a 29-year-old patient. The authors highlight the importance of hemostatic agents and primary wound closure and the role of vascular embolization as a potential tool for preventing hemorrhage in these cases.
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http://dx.doi.org/10.1097/SCS.0000000000007611DOI Listing
March 2021

Loliolide, a New Therapeutic Option for Neurological Diseases? In Vitro Neuroprotective and Anti-Inflammatory Activities of a Monoterpenoid Lactone Isolated from .

Int J Mol Sci 2021 Feb 14;22(4). Epub 2021 Feb 14.

MARE-Marine and Environmental Sciences Centre, ESTM, Polytechnic of Leiria, 2520-614 Peniche, Portugal.

Parkinsons Disease (PD) is the second most common neurodegenerative disease worldwide, and is characterized by a progressive degeneration of dopaminergic neurons. Without an effective treatment, it is crucial to find new therapeutic options to fight the neurodegenerative process, which may arise from marine resources. Accordingly, the goal of the present work was to evaluate the ability of the monoterpenoid lactone Loliolide, isolated from the green seaweed , to prevent neurological cell death mediated by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y cells and their anti-inflammatory effects in RAW 264.7 macrophages. Loliolide was obtained from the diethyl ether extract, purified through column chromatography and identified by NMR spectroscopy. The neuroprotective effects were evaluated by the MTT method. Cells' exposure to 6-OHDA in the presence of Loliolide led to an increase of cells' viability in 40%, and this effect was mediated by mitochondrial protection, reduction of oxidative stress condition and apoptosis, and inhibition of the NF-kB pathway. Additionally, Loliolide also suppressed nitric oxide production and inhibited the production of TNF-α and IL-6 pro-inflammatory cytokines. The results suggest that Loliolide can inspire the development of new neuroprotective therapeutic agents and thus, more detailed studies should be considered to validate its pharmacological potential.
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http://dx.doi.org/10.3390/ijms22041888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918146PMC
February 2021

Fighting Bisphenol A-Induced Male Infertility: The Power of Antioxidants.

Antioxidants (Basel) 2021 Feb 15;10(2). Epub 2021 Feb 15.

Department of Medical Sciences, Institute of Biomedicine-iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal.

Bisphenol A (BPA), a well-known endocrine disruptor present in epoxy resins and polycarbonate plastics, negatively disturbs the male reproductive system affecting male fertility. In vivo studies showed that BPA exposure has deleterious effects on spermatogenesis by disturbing the hypothalamic-pituitary-gonadal axis and inducing oxidative stress in testis. This compound seems to disrupt hormone signalling even at low concentrations, modifying the levels of inhibin B, oestradiol, and testosterone. The adverse effects on seminal parameters are mainly supported by studies based on urinary BPA concentration, showing a negative association between BPA levels and sperm concentration, motility, and sperm DNA damage. Recent studies explored potential approaches to treat or prevent BPA-induced testicular toxicity and male infertility. Since the effect of BPA on testicular cells and spermatozoa is associated with an increased production of reactive oxygen species, most of the pharmacological approaches are based on the use of natural or synthetic antioxidants. In this review, we briefly describe the effects of BPA on male reproductive health and discuss the use of antioxidants to prevent or revert the BPA-induced toxicity and infertility in men.
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http://dx.doi.org/10.3390/antiox10020289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919053PMC
February 2021

Unravelling the Dermatological Potential of the Brown Seaweed .

Mar Drugs 2021 Feb 28;19(3). Epub 2021 Feb 28.

MARE-Marine and Environmental Sciences Centre, ESTM, Polytechnic of Leiria, 2520-614 Peniche, Portugal.

The ever-increasing interest in keeping a young appearance and healthy skin has leveraged the skincare industry. This, coupled together with the increased concern regarding the safety of synthetic products, has boosted the demand for new and safer natural ingredients. Accordingly, the aim of this study was to evaluate the dermatological potential of the brown seaweed The antioxidant, anti-enzymatic, antimicrobial, photoprotective and anti-inflammatory properties of five fractions (F1-F5) were evaluated. The ethyl acetate fraction (F3) demonstrated the most promising results, with the best ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals (EC of 140.1 µg/mL) and the capacity to reduce reactive oxygen species (ROS) production promoted by UVA and UVB radiation in 3T3 cells, revealing its antioxidant and photoprotective potential. This fraction also exhibited the highest anti-enzymatic capacity, inhibiting the activities of collagenase, elastase and tyrosinase (IC of 7.2, 4.8 and 85.9 µg/mL, respectively). Moreover, F3 showed anti-inflammatory potential, reducing TNF-α and IL-6 release induced by LPS treatment in RAW 264.7 cells. These bioactivities may be related to the presence of phenolic compounds, such as phlorotannins, as demonstrated by NMR analysis. The results highlight the potential of as a source of bioactive ingredients for further dermatological applications.
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http://dx.doi.org/10.3390/md19030135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997182PMC
February 2021

Microalgae n-3 PUFAs Production and Use in Food and Feed Industries.

Mar Drugs 2021 Feb 18;19(2). Epub 2021 Feb 18.

GREENTECH, Biopôle Clermont-Limagne, 63360 SAINT BEAUZIRE, France.

N-3 polyunsaturated fatty acids (n-3 PUFAs), and especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential compounds for human health. They have been proven to act positively on a panel of diseases and have interesting anti-oxidative, anti-inflammatory or anti-cancer properties. For these reasons, they are receiving more and more attention in recent years, especially future food or feed development. EPA and DHA come mainly from marine sources like fish or seaweed. Unfortunately, due to global warming, these compounds are becoming scarce for humans because of overfishing and stock reduction. Although increasing in recent years, aquaculture appears insufficient to meet the increasing requirements of these healthy molecules for humans. One alternative resides in the cultivation of microalgae, the initial producers of EPA and DHA. They are also rich in biochemicals with interesting properties. After defining macro and microalgae, this review synthesizes the current knowledge on n-3 PUFAs regarding health benefits and the challenges surrounding their supply within the environmental context. Microalgae n-3 PUFA production is examined and its synthesis pathways are discussed. Finally, the use of EPA and DHA in food and feed is investigated. This work aims to define better the issues surrounding n-3 PUFA production and supply and the potential of microalgae as a sustainable source of compounds to enhance the food and feed of the future.
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http://dx.doi.org/10.3390/md19020113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922858PMC
February 2021

Supramolecular ultra-short carboxybenzyl-protected dehydropeptide-based hydrogels for drug delivery.

Mater Sci Eng C Mater Biol Appl 2021 Mar 8;122:111869. Epub 2021 Jan 8.

Centre of Chemistry (CQUM), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal. Electronic address:

Self-assembled peptide-based hydrogels are promising materials for biomedical research owing to biocompatibility and similarity to the extracellular matrix, amenable synthesis and functionalization and structural tailoring of the rheological properties. Wider developments of self-assembled peptide-based hydrogels in biomedical research and clinical translation are hampered by limited commercial availability allied to prohibitive costs. In this work a focused library of Cbz-protected dehydrodipeptides Cbz-L-Xaa-Z-ΔPhe-OH (Xaa= Met, Phe, Tyr, Ala, Gly) was synthesised and evaluated as minimalist hydrogels. The Cbz-L-Met-Z-ΔPhe-OH and Cbz-L-Phe-Z-ΔPhe-OH hydrogelators were comprehensively evaluated regarding molecular aggregation and self-assembly, gelation, biocompatibility and as drug carriers for delivery of the natural compound curcumin and the clinically important antitumor drug doxorubicin. Drug release profiles and FRET studies of drug transport into small unilamellar vesicles (as biomembrane models) demonstrated that the Cbz-protected dehydropeptide hydrogels are effective nanocarriers for drug delivery. The expedite and scalable synthesis (in 3 steps), using commercially available reagents and amenable reaction conditions, makes Cbz-protected dehydrodipeptide hydrogels, widely available at affordable cost to the research community.
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http://dx.doi.org/10.1016/j.msec.2021.111869DOI Listing
March 2021

Polar lipidomic profile shows Chlorococcum amblystomatis as a promising source of value-added lipids.

Sci Rep 2021 Feb 23;11(1):4355. Epub 2021 Feb 23.

Department of Chemistry, Mass Spectrometry Centre, LAQV REQUIMTE, University of Aveiro, Santiago University Campus, 3810-193, Aveiro, Portugal.

There is a growing trend to explore microalgae as an alternative resource for the food, feed, pharmaceutical, cosmetic and fuel industry. Moreover, the polar lipidome of microalgae is interesting because of the reports of bioactive polar lipids which could foster new applications for microalgae. In this work, we identified for the first time the Chlorococcum amblystomatis lipidome using hydrophilic interaction liquid chromatography-high resolution electrospray ionization- tandem mass spectrometry (HILIC-HR-ESI-MS/MS). The Chlorococcum amblystomatis strain had a lipid content of 20.77% and the fatty acid profile, determined by gas chromatography-mass spectrometry, has shown that this microalga contains high amounts of omega-3 polyunsaturated fatty acids (PUFAs). The lipidome identified included 245 molecular ions and 350 lipid species comprising 15 different classes of glycolipids (6), phospholipids (7) and betaine lipids (2). Of these, 157 lipid species and the main lipid species of each class were esterified with omega-3 PUFAs. The lipid extract has shown antioxidant activity and anti-inflammatory potential. Lipid extracts also had low values of atherogenic (0.54) and thrombogenic index (0.27). In conclusion, the lipid extracts of Chlorococcum amblystomatis have been found to be a source of lipids rich in omega-3 PUFAs for of great value for the food, feed, cosmetic, nutraceutical and pharmaceutical industries.
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http://dx.doi.org/10.1038/s41598-021-83455-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902829PMC
February 2021

Association of venous thromboembolic events with skin, pulmonary and kidney involvement in ANCA-associated vasculitis: a multinational study.

Rheumatology (Oxford) 2021 Feb 1. Epub 2021 Feb 1.

Department of Medicine, University of Cambridge, Cambridge, UK.

Objective: To investigate the occurrence of venous thromboembolic events (VTE) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, Turkey, Russia, UK, and North America.

Methods: Patients with a definite diagnosis of AAV who were followed for at least 3 months and had sufficient documentation were included. Data on VTE, including either deep vein thrombosis or pulmonary embolism, were collected retrospectively from tertiary vasculitis centers. Univariate and multivariate regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Over a median follow up of 63 (29; 101) months, VTE occurred in 278 (9.7%) of 2869 AAV patients with a similar frequency across different countries (from 6.3% to 13.7%), and AAV subtype (granulomatosis with polyangiitis: 9.8%; 95% CI 8.3-11.6, microscopic polyangiitis: 9.6%; 95% CI 7.9-11.4, and eosinophilic granulomatosis with polyangiitis: 9.8%; 95% CI 7.0-13.3). Most VTE (65.6%) were reported in the first-year post diagnosis. Multiple factor logistic regression analysis adjusted for sex and age showed that skin (OR 1.71, 95% CI 1.01-2.92), pulmonary (OR 1.78, 95% CI 1.04-3.14) and kidney involvement (eGFR 15-60 mL/min/1.73 m2, OR 2.86, 95% CI 1.27-6.47; eGFR < 15 mL/min/1.73 m2, OR 6.71, 95% CI 2.94-15.33) were independent variables associated with a higher occurrence of VTE.

Conclusion: Two thirds of VTE occurred during the initial phase of active disease. We confirmed previous findings from smaller studies that a decrease in kidney function, skin involvement and pulmonary disease are independently associated with VTE.
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http://dx.doi.org/10.1093/rheumatology/keab071DOI Listing
February 2021

Maternal and fetal outcomes of pregnancy in chronic kidney disease: diagnostic challenges, surveillance and treatment throughout the spectrum of kidney disease.

J Bras Nefrol 2021 Jan-Mar;43(1):88-102

Serviço de Ginecologia e Obstetrícia do Centro Hospitalar de Vila Nova de Gaia e Espinho, Portugal.

Pregnancy requires several physiological adaptations from the maternal organism, including modifications in the glomerular filtration rate and renal excretion of several products. Chronic kidney disease (CKD) can negatively affect these modifications and consequently is associated with several adverse maternal and fetal adverse outcomes (gestational hypertension, progression of renal disease, pre-eclampsia, fetal growth restriction, and preterm delivery). A multidisciplinary vigilance of these pregnancies is essential in order to avoid and/or control the harmful effects associated with this pathology. Dialysis and transplantation can decrease the risks of maternal and fetal complications, nonetheless, the rates of complications remain high comparing with a normal pregnancy. Several recent developments in this area have improved quality and efficacy of treatment of pregnant women with CKD. This article summarizes the most recent literature about CKD and pregnancy.
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http://dx.doi.org/10.1590/2175-8239-JBN-2020-0055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061969PMC
March 2020

Chikungunya arthritis - should we expect it to become more common in Portuguese rheumatology?

Acta Reumatol Port 2020 Oct-Dec;45(4):298-300

Hospital de Braga.

Chikungunya virus is known to cause acute disease characterized by fever, rash, myalgias, conjunctivitis and arthritis, having potential to cause chronic musculoskeletal disease, namely persistent arthritis. The area of spread of the virus in the world has been increasing and the migratory flows make the occurrence of Chikungunya induced chronic arthritis more and more scattered. Data regarding the experience of Portuguese rheumatology centres in identifying and treating chronic ChikV induced arthritis are not available. The authors describe the diagnosis and treatment aspects of three cases of "imported" Chikungunya induced chronic arthritis, briefly discuss its approach in the light of current knowledge and alert to the possibility this situation may become more prevalent in the Portuguese rheumatology setting.
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January 2021

Septic arthritis: a 5-year review of admissions to the Orthopedic Department.

Acta Reumatol Port 2020 Oct-Dec;45(4):253-258

ULSAM.

Objectives: Characterization of sociodemographic and clinical aspects of patients admitted to the Orthopedic Department (OD) after observation in the Emergency Room (ER) with the diagnosis of septic arthritis (SA).

Material And Methods: A retrospective, monocentric, cross-sectional study was conducted. Sociodemographic and clinical data on patients admitted to the OD with suspected SA between April 2014 and September 2019 were collected.

Results: One-hundred and ten patients were included. In the overall sample, most patients were male (n=61; 55.5%) with a median age of 70 (IQR=20) years old. Thirty-six patients (32.7%) had a previous history of hyperuricemia or gout, or had this diagnosis established at the time of their hospital admission. Monoarthritis was the most common form of presentation (n=106; 96.4%), with the knee being the most frequently involved joint (n=60; 54.5%). S. aureus was the most representative microorganism in synovial fluid (SF) cultures (n=33; 30.6%). SF cultures did not allow the identification of a causative microorganism in 53 cases submitted to arthrotomy (50.5%). Serum C-reactive protein (CRP) was a predictive factor for microorganism identification in SF cultures, with values ≥ 17.6 mg/dl presenting a sensibility and specificity of 60.8% and 77.4%, respectively [CI 95% (0.52 - 0.80)]. Patients with a diagnosis of hyperuricemia or gout presented a higher risk for a negative SF culture result (OR = 4.7 [CI 95% =1.9 - 11.5]).

Conclusions: Elderly subjects with multiple comorbidities, namely cardiovascular risk factors, seem more prone to SA. Serum CRP appears to be a predictive factor for the identification of a causative microorganism. The higher risk of a negative SF culture in patients with hyperuricemia or gout should alert us for the possibility of misdiagnosis of SA in patients with an acute gout attack.
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January 2021

Acinetobacter spp. in food and drinking water - A review.

Food Microbiol 2021 May 7;95:103675. Epub 2020 Nov 7.

Universidade Católica Portuguesa, CBQF - Centro de Biotecnologia e Química Fina - Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005, Porto, Portugal. Electronic address:

Acinetobacter spp. has emerged as a pathogen of major public health concern due to their increased resistance to antibiotics and their association with a wide range of nosocomial infections, community-acquired infections and war and natural disaster-related infections. It is recognized as a ubiquitous organism however, information about the prevalence of different pathogenic species of this genus in food sources and drinking water is scarce. Since the implementation of molecular techniques, the role of foods as a source of several species, including the Acinetobacter baumannii group, has been elucidated. Multidrug resistance was also detected among Acinetobacter spp. isolated from food products. This highlights the importance of foods as potential sources of dissemination of Acinetobacter spp. between the community and clinical environments and reinforces the need for further investigations on the potential health risks of Acinetobacter spp. as foodborne pathogens. The aim of this review was to summarize the published data on the occurrence of Acinetobacter spp. in different food sources and drinking water. This information should be taken into consideration by those responsible for infection control in hospitals and other healthcare facilities.
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http://dx.doi.org/10.1016/j.fm.2020.103675DOI Listing
May 2021

Impact of Citrate and Lipid-Functionalized Magnetic Nanoparticles in Dehydropeptide Supramolecular Magnetogels: Properties, Design and Drug Release.

Nanomaterials (Basel) 2020 Dec 23;11(1). Epub 2020 Dec 23.

Centro de Física (CFUM), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.

Currently, the nanoparticle functionalization effect on supramolecular peptide-based hydrogels remains undescribed, but is expected to affect the hydrogels' self-assembly and final magnetic gel properties. Herein, two different functionalized nanoparticles: citrate-stabilized (14.4 ± 2.6 nm) and lipid-coated (8.9 ± 2.1 nm) magnetic nanoparticles, were used for the formation of dehydropeptide-based supramolecular magnetogels consisting of the ultra-short hydrogelator Cbz-L-Met--ΔPhe-OH, with an assessment of their effect over gel properties. The lipid-coated nanoparticles were distributed along the hydrogel fibers, while citrate-stabilized nanoparticles were aggregated upon gelation, which resulted into a heating efficiency improvement and decrease, respectively. Further, the lipid-coated nanoparticles did not affect drug encapsulation and displayed improved drug release reproducibility compared to citrate-stabilized nanoparticles, despite the latter attaining a stronger AMF-trigger. This report points out that adsorption of nanoparticles to hydrogel fibers, which display domains that improve or do not affect drug encapsulation, can be explored as a means to optimize the development of supramolecular magnetogels to advance theranostic applications.
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http://dx.doi.org/10.3390/nano11010016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824179PMC
December 2020