Publications by authors named "Andreia Silva"

168 Publications

Skin aquaporins as druggable targets: Promoting health by addressing the disease.

Biochimie 2021 Jun 4. Epub 2021 Jun 4.

Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003, Lisboa, Portugal; Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, 1649-003, Lisboa, Portugal. Electronic address:

Skin is the most vulnerable organ of the human body since it is the first line of defense, covering the entire external body surface. Additionally, skin has a critical role in thermoregulation, sensation, immunological surveillance, and biochemical processes such as Vitamin D production by ultraviolet irradiation. The ability of the skin layers and resident cells to maintain skin physiology, such as hydration, regulation of keratinocytes proliferation and differentiation and wound healing, is supported by key proteins such as aquaporins (AQPs) that facilitate the movements of water and small neutral solutes across membranes. Various AQP isoforms have been detected in different skin-resident cells where they perform specific roles, and their dysregulation has been associated with several skin pathologies. This review summarizes the current knowledge of AQPs involvement in skin physiology and pathology, highlighting their potential as druggable targets for the treatment of skin disorders.
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http://dx.doi.org/10.1016/j.biochi.2021.05.019DOI Listing
June 2021

Mitochondrial Functional Assessment in Mammalian Gametes Using Fluorescent Probes.

Methods Mol Biol 2021 ;2310:57-68

CNC-Center for Neuroscience and Cell Biology, CIBB, Polo 3, University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-504, Coimbra, Portugal.

A positive relationship between mitochondrial functionality and gamete quality, ultimately contributing to fertilization success and normal embryo development has been established for some years now. Both mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production are major indicators of mitochondrial function, and the need for accurate biomarkers mirroring gamete quality highlights the importance of a precise assessment of mitochondrial quality and function. In this chapter, we discuss the use of some mitochondrial fluorescent probes coupled to flow cytometry and/or fluorescence microscopy to specifically assess mitochondrial ROS production and MMP in both sperm and oocytes. Furthermore, as the distribution/aggregation of mitochondria in the oocyte is of interest to determine its quality, a detailed protocol is also given. These methodologies are easy, accurate and can be safely applied in research- and/or clinical-based contexts.
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http://dx.doi.org/10.1007/978-1-0716-1433-4_5DOI Listing
January 2021

Genetic atypical hemolytic uremic syndrome in children: a 20-year experience from a tertiary center.

J Bras Nefrol 2021 May 12. Epub 2021 May 12.

Centro Hospitalar Universitário do Porto, Centro Materno-Infantil do Norte, Unidade de Nefrologia Pediátrica, Porto, Portugal.

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare disorder characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, which primarily affects preschool-aged children. This study's aim was to describe the clinical profile, management, and long-term outcome of the genetic aHUS patients admitted to a tertiary care pediatric nephrology center during 20 years.

Methods: We performed a retrospective analysis of the clinical records of all aHUS patients younger than 18 years with identified genetic mutations. Data on clinical features, genetic study, therapeutic interventions, and long-term outcomes were reviewed.

Results: Five cases of aHUS with an identified genetic mutation were included; all were inaugural cases with the youngest being 4 months old. Complement factor H gene mutation was identified in four patients. Therapeutic plasma exchange was performed for acute management in 4 patients, one of whom also needed acute renal replacement therapy (peritoneal dialysis). All patients went on complete remission, 2 had more than one relapse but only 1 of these progressed to chronic kidney disease during the follow-up period (median (25th-75th percentile), 136 (43.5-200.5) months).

Conclusion: In children, the prognosis of renal function seems to be strongly dependent on the genetic background, thus being crucial to perform genetic study in all aHUS cases. In our cohort, 2 patients presented genetic mutations not previously described. Recent innovations on the genetic field leading to the identification of new mutations has lead to a better understanding of aHUS pathogenesis, but further studies, focusing on the genotype-phenotype correlation, with longer follow-up periods, are needed.
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http://dx.doi.org/10.1590/2175-8239-JBN-2020-0199DOI Listing
May 2021

Computer-aided autism diagnosis based on visual attention models using eye tracking.

Sci Rep 2021 May 12;11(1):10131. Epub 2021 May 12.

School of Arts, Sciences and Humanities (EACH), University of Sao Paulo (USP), Sao Paulo, SP, 03828-000, Brazil.

An advantage of using eye tracking for diagnosis is that it is non-invasive and can be performed in individuals with different functional levels and ages. Computer/aided diagnosis using eye tracking data is commonly based on eye fixation points in some regions of interest (ROI) in an image. However, besides the need for every ROI demarcation in each image or video frame used in the experiment, the diversity of visual features contained in each ROI may compromise the characterization of visual attention in each group (case or control) and consequent diagnosis accuracy. Although some approaches use eye tracking signals for aiding diagnosis, it is still a challenge to identify frames of interest when videos are used as stimuli and to select relevant characteristics extracted from the videos. This is mainly observed in applications for autism spectrum disorder (ASD) diagnosis. To address these issues, the present paper proposes: (1) a computational method, integrating concepts of Visual Attention Model, Image Processing and Artificial Intelligence techniques for learning a model for each group (case and control) using eye tracking data, and (2) a supervised classifier that, using the learned models, performs the diagnosis. Although this approach is not disorder-specific, it was tested in the context of ASD diagnosis, obtaining an average of precision, recall and specificity of 90%, 69% and 93%, respectively.
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http://dx.doi.org/10.1038/s41598-021-89023-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115570PMC
May 2021

A hafnium-based metal-organic framework for the entrapment of molybdenum hexacarbonyl and the light-responsive release of the gasotransmitter carbon monoxide.

Mater Sci Eng C Mater Biol Appl 2021 May 25;124:112053. Epub 2021 Mar 25.

CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal. Electronic address:

A carbon monoxide-releasing material (CORMA) has been prepared by inclusion of molybdenum hexacarbonyl in a hafnium-based metal-organic framework (MOF) with the UiO-66 architecture. Mo(CO) was adsorbed from solution to give supported materials containing 6.0-6.6 wt% Mo. As confirmed by powder X-ray diffraction (PXRD) and SEM coupled with energy dispersive X-ray spectroscopy, neither the crystallinity nor the morphology of the porous host was affected by the loading process. While the general shape of the N physisorption isotherms (77 K) did not change significantly after encapsulation of Mo(CO), the micropore volume decreased by ca. 20%. Thermogravimetric analysis of the as-prepared materials revealed a weight loss step around 160 °C associated with the decomposition of Mo(CO) to subcarbonyl species. Confirmation for the presence of encapsulated Mo(CO) complexes was provided by FT-IR and C{H} cross-polarization magic-angle spinning NMR spectroscopies. To test the capability of these materials to behave as CORMAs and transfer CO to heme proteins, the standard myoglobin (Mb) assay was used. While stable in the dark, photoactivation with low-power UV light (365 nm) liberated CO from the encapsulated hexacarbonyl molecules in Mo(6.0)/UiO-66(Hf), leading to a maximum amount of 0.26 mmol CO released per gram of material. Under the simulated physiological conditions of the Mb assay (37 °C, pH 7.4 buffer), minimal leaching of molybdenum occurred, PXRD showed only slight amorphization, and FT-IR spectroscopy confirmed the high chemical stability of the MOF host.
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http://dx.doi.org/10.1016/j.msec.2021.112053DOI Listing
May 2021

Quadratus Lumborum block as primary anesthetic technique for colostomy procedure: a case report.

Braz J Anesthesiol 2021 Apr 20. Epub 2021 Apr 20.

Tondela-Viseu Hospital Centre, Department of Anesthesiology, Viseu, Portugal.

An elderly patient was admitted to the hospital due to an enterovesical fistula and a terminal colostomy was proposed. The patient had a high anesthetic risk and thus a quadratus lumborum block was chosen as the sole anesthetic technique. This block has been described to provide both somatic and visceral analgesia to the abdomen. In fact, it yielded good anesthetic conditions to perform the procedure and allowed the patient to be hemodynamically stable and comfortable throughout the case. The postoperative period was uneventful.
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http://dx.doi.org/10.1016/j.bjane.2021.03.014DOI Listing
April 2021

Data sharing in PredRet for accurate prediction of retention time: Application to plant food bioactive compounds.

Food Chem 2021 Apr 9;357:129757. Epub 2021 Apr 9.

Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal; Instituto de Biologia Experimental Tecnológica, Av. da República, Quinta do Marquês, Edificio iBET/ITQB, 2780-157 Oeiras, Portugal; Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Avenida Professor Gama Pinto, 1649-003 Lisbon, Portugal.

Prediction of retention times (RTs) is increasingly considered in untargeted metabolomics to complement MS/MS matching for annotation of unidentified peaks. We tested the performance of PredRet (http://predret.org/) to predict RTs for plant food bioactive metabolites in a data sharing initiative containing entry sets of 29-103 compounds (totalling 467 compounds, >30 families) across 24 chromatographic systems (CSs). Between 27 and 667 predictions were obtained with a median prediction error of 0.03-0.76 min and interval width of 0.33-8.78 min. An external validation test of eight CSs showed high prediction accuracy. RT prediction was dependent on shape and type of LC gradient, and number of commonly measured compounds. Our study highlights PredRet's accuracy and ability to transpose RT data acquired from one CS to another CS. We recommend extensive RT data sharing in PredRet by the community interested in plant food bioactive metabolites to achieve a powerful community-driven open-access tool for metabolomics annotation.
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http://dx.doi.org/10.1016/j.foodchem.2021.129757DOI Listing
April 2021

Extracellular vesicles for tissue repair and regeneration: evidence, challenges and opportunities.

Adv Drug Deliv Rev 2021 Apr 16. Epub 2021 Apr 16.

Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Department of Materials, Imperial College London, London, UK; Department of Bioengineering, Imperial College London, London, UK; Institute of Biomedical Engineering, Imperial College London, London, UK. Electronic address:

Extracellular vesicles (EVs) are biological nanoparticles naturally secreted by cells, acting as delivery vehicles for molecular messages. During the last decade, EVs have been assigned multiple functions that have established their potential as therapeutic mediators for a variety of diseases and conditions. In this review paper, we report on the potential of EVs in tissue repair and regeneration. The regenerative properties that have been associated with EVs are explored, detailing the molecular cargo they carry that is capable of mediating such effects, the signaling cascades triggered in target cells and the functional outcome achieved. EV interactions and biodistribution in vivo that influence their regenerative effects are also described, particularly upon administration in combination with biomaterials. Finally, we review the progress that has been made for the successful implementation of EV regenerative therapies in a clinical setting.
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http://dx.doi.org/10.1016/j.addr.2021.04.013DOI Listing
April 2021

Comparative study on the local tolerance and efficacy of benzalkonium chloride, myristalkonium chloride and nonoxynol-9 as active principles in vaginal contraceptives.

Eur J Contracept Reprod Health Care 2021 Apr 6:1-9. Epub 2021 Apr 6.

Biology of Reproduction and Stem Cells Group, CNC- Center for Neuroscience and Cell Biology, CIBB, Polo III, Azinhaga Santa Comba, University of Coimbra, Coimbra, Portugal.

Background: Spermicides have been identified as a potentially attractive alternative to hormonal contraceptives and/or intrauterine devices. Thus, this study aimed evaluating the efficacy and local tolerance of benzalkonium chloride (BKC) and myristalkonium chloride (MKC) contained in Pharmatex vaginal formulations and compare them with nonoxynol-9 (N-9), the most common active ingredient in topical vaginal contraceptives.

Methods: Human normozoospermic samples were assessed for motility, viability, acrosome status and penetration ability after exposure to control, N-9 or different BKC and MKC doses for 0 and 10 minutes. Local tolerance on HeLa cells was evaluated by the Trypan-blue and MTT assays.

Results: Exposure to BKC and MKC reduced acrosome integrity while promoting total immobilisation and complete loss of sperm viability ( < .001,  = 15). Both compounds also compromised sperm penetration ability upon exposure ( < .001,  = 15). N-9 induced the same outcomes ( < .001,  = 15); nevertheless, it was more toxic to HeLa cells than BKC and MKC ( < .05,  = 14).

Conclusions: BKC and MKC present strong spermicidal activity at lower doses than N-9 and were better tolerated after immediate exposure than N-9. Available Pharmatex galenic formulations were as effective as products based on N-9.
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http://dx.doi.org/10.1080/13625187.2021.1900563DOI Listing
April 2021

Strategies to Broaden the Applications of Olive Biophenols Oleuropein and Hydroxytyrosol in Food Products.

Antioxidants (Basel) 2021 Mar 13;10(3). Epub 2021 Mar 13.

LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.

Oleuropein (OLE) and hydroxytyrosol (HT) are olive-derived phenols recognised as health-promoting agents with antioxidant, anti-inflammatory, cardioprotective, antifungal, antimicrobial, and antitumor activities, providing a wide range of applications as functional food ingredients. HT is Generally Recognised as Safe (GRAS) by the European Food Safety Authority (EFSA) and the Food and Drug Administration (FDA), whereas OLE is included in EFSA daily consumptions recommendations, albeit there is no official GRAS status for its pure form. Their application in food, however, may be hindered by challenges such as degradation caused by processing conditions and undesired sensorial properties (e.g., the astringency of OLE). Among the strategies to overcome such setbacks, the encapsulation in delivery systems and the covalent and non-covalent complexation are highlighted in this review. Additionally, the synthesis of OLE and HT derivatives are studied to improve their applicability. All in all, more research needs however to be carried out to investigate the impact of these approaches on the sensory properties of the final food product and its percussions at the gastrointestinal level, as well as on bioactivity. At last limitations of these approaches at a scale of the food industry must also be considered.
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http://dx.doi.org/10.3390/antiox10030444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000085PMC
March 2021

Salivary BPIFA proteins are altered in patients undergoing hematopoietic cell transplantation.

Oral Dis 2021 Mar 7. Epub 2021 Mar 7.

Department of Oral Diagnosis, School of Dentistry of Piracicaba, University of Campinas (FOP/UNICAMP), Piracicaba, São Paulo, Brazil.

Objective: The aim of this study was to evaluate the expression of BPIFA proteins in the saliva and salivary glands of hematopoietic cell transplant (HCT) patients.

Material And Methods: This longitudinal study included patients who had undergone autologous HCT (auto-HCT) and allogeneic HCT (allo-HCT), and unstimulated saliva was collected at three time points, with a fourth collection at oral chronic graft-versus-host disease (cGVHD) onset. BPIFA expression was analysed by Western blotting in saliva and immunostaining in the minor salivary glands of cGVHD patients.

Results: Auto-HCT patients showed increased levels of BPIFA1 (p = .021) and BPIFA2 at D+7 (p = .040), whereas allo-HCT group demonstrated decreased expression of BPIFA2 at D+8 (p = .002) and at D+80 (p = .001) and a significant association between BPIFA2 low levels and hyposalivation was observed (p = .02). BPIFA2 was significantly lower in the cGVHD patients when compared to baseline (p = .04).

Conclusions: The results of this study show distinct pattern of expression of BPIF proteins in both auto-HCT and allo-HCT recipients with decreased levels of BPIFA2 during hyposalivation and cGVHD. Further studies are necessary to elucidate these proteins mechanisms and their clinical implications in these groups of patients.
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http://dx.doi.org/10.1111/odi.13832DOI Listing
March 2021

A high-throughput Galectin-9 imaging assay for quantifying nanoparticle uptake, endosomal escape and functional RNA delivery.

Commun Biol 2021 Feb 16;4(1):211. Epub 2021 Feb 16.

Advanced Drug Delivery, Pharmaceutical Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

RNA-based therapies have great potential to treat many undruggable human diseases. However, their efficacy, in particular for mRNA, remains hampered by poor cellular delivery and limited endosomal escape. Development and optimisation of delivery vectors, such as lipid nanoparticles (LNPs), are impeded by limited screening methods to probe the intracellular processing of LNPs in sufficient detail. We have developed a high-throughput imaging-based endosomal escape assay utilising a Galectin-9 reporter and fluorescently labelled mRNA to probe correlations between nanoparticle-mediated uptake, endosomal escape frequency, and mRNA translation. Furthermore, this assay has been integrated within a screening platform for optimisation of lipid nanoparticle formulations. We show that Galectin-9 recruitment is a robust, quantitative reporter of endosomal escape events induced by different mRNA delivery nanoparticles and small molecules. We identify nanoparticles with superior escape properties and demonstrate cell line variances in endosomal escape response, highlighting the need for fine-tuning of delivery formulations for specific applications.
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http://dx.doi.org/10.1038/s42003-021-01728-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887203PMC
February 2021

The 1G/1G+1G/2G Genotypes of rs1799750 Are Associated with Higher Levels of MMP-1 and Are Both Associated with Lipodystrophy in People Living with HIV on Antiretroviral Therapy.

AIDS Res Hum Retroviruses 2021 05 22;37(5):399-406. Epub 2021 Mar 22.

Faculty of Medical Sciences (FCM), University of Pernambuco (UPE), Recife, Brazil.

In HIV-infected patients, antiretroviral therapy (ART) is associated to adipose tissue redistribution known as lipodystrophy (LD). This study aimed at verifying the association between the polymorphism of the gene (rs1799750) (1G/2G) and the serum levels of matrix metalloproteinase 1 (MMP-1) with LD and its subtypes in people living with HIV on ART. This is a cross-secional study. LD was self-reported. The determination of the rs1799750 gene polymorphism was performed by real-time PCR, and the serum concentrations of MMP-1 were quantified by the enzyme-linked immunosorbent assay (ELISA) method. Of 404 participants, 204 (51%) were diagnosed with LD, of whom 89 (43%) had mixed lipodystrophy (ML), 72 (35%) had lipohypertrophy (LH), and 43 (22%) had lipoatrophy (LA). There was an association between the genotypes 1G/1G+1G/2G and higher serum levels of MMP-1 ( = .025). There was no association of (1G/2G) with LD. Other factors associated with LD were current CD4 ≤ 350 [odds ratio (OR) = 4.85, confidence interval (CI) = 1.78-47.99,  = .0033] and serum MMP-1 levels >6.81 (OR = 2.67, CI = 1.21-6.08,  = .0165). Factors associated with ML: current CD4 ≤ 350 (OR = 5.59, CI = 1.69-20.39,  = .006); with LH: number of antiretroviral regimens used: 2 (OR = 2.06, CI = 1.01-4.20,  = .0460) and 3+ (OR = 2.09, CI = 1.00-4.35,  = .0477), and current CD4 ≤ 350 (OR = 2.08, CI = 1.00-4.24,  = .0461); and with LA: current viral load >40 (OR = 2.52, CI = 1.03-5.91,  = .0372) and current use of zidovudine (OR = 2.97, CI = 1.32-6.54,  = .0074). Higher levels of MMP-1 were associated with genotypes 1G/2G+1G/1G and with LD. Other individual risk factors were independently associated with LD, and its subtypes, suggesting that the pathogenesis itself is differently manifested for each type of LD.
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http://dx.doi.org/10.1089/AID.2020.0237DOI Listing
May 2021

Effect of growth differentiation factor 9 (GDF-9) on in vitro development of collared peccary preantral follicles in ovarian tissues.

Anim Reprod Sci 2021 Mar 5;226:106717. Epub 2021 Feb 5.

Laboratory of Animal Germplasm Conservation, Federal Rural University of Semi-Arid, Mossoró, RN, Brazil. Electronic address:

The aims were to identify the effects of growth differentiation factor 9 (GDF-9) on the in vitro development of ovarian preantral follicles (PAFs) of collared peccaries. Ovarian fragments were in vitro cultured for 1 or 7 days without or with inclusion of GDF-9 in the medium (0, 50, 100, or 200 ng/mL). The non-cultured (control) and cultured fragments were evaluated for PAF viability, activation, and cell proliferation. Although there were no differences in the percentage of morphologically normal follicles, the percentage of growing follicles was greater compared to the control in all treatment groups, especially those cultured with 200 ng/mL GDF-9 for 7 days (P < 0.05). The inclusion of GDF-9 in the medium did not interfere with PAF viability (P> 0.05); however, treatment with 200 ng/mL GDF-9 resulted in greater (P < 0.05) cell proliferation in PAFs cultured for 1 or 7 days (∼2.5 nucleolar organizing regions - NORs) compared to the follicles of the control group (2.0 NORs). In addition, peccary ovarian cortexes were subjected to PCR analysis and there was detection of the mRNA GDF-9 receptor transcripts of the BMPR2 (type I receptor) and ALK-5 (type II receptor) types. In conclusion, GDF-9, especially at a 200 ng/mL inclusion in the culture medium, was actively involved in the in vitro development of collared peccary PAFs.
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http://dx.doi.org/10.1016/j.anireprosci.2021.106717DOI Listing
March 2021

Selection of Fluorescent, Bioluminescent, and Radioactive Tracers to Accurately Reflect Extracellular Vesicle Biodistribution .

ACS Nano 2021 02 20;15(2):3212-3227. Epub 2021 Jan 20.

Discovery Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg 43150, Sweden.

The ability to track extracellular vesicles (EVs) without influencing their biodistribution is a key requirement for their successful development as drug delivery vehicles and therapeutic agents. Here, we evaluated the effect of five different optical and nuclear tracers on the biodistribution of EVs. Expi293F EVs were labeled using either a noncovalent fluorescent dye DiR, or covalent modification with indium-DTPA, or bioengineered with fluorescent (mCherry) or bioluminescent (Firefly and NanoLuc luciferase) proteins fused to the EV marker, CD63. To focus specifically on the effect of the tracer, we compared EVs derived from the same cell source and administered systemically by the same route and at equal dose into tumor-bearing BALB/c mice. Indium and DiR were the most sensitive tracers for imaging of EVs, providing the most accurate quantification of vesicle biodistribution by imaging of organs and analysis of tissue lysates. Specifically, NanoLuc fused to CD63 altered EV distribution, resulting in high accumulation in the lungs, demonstrating that genetic modification of EVs for tracking purposes may compromise their physiological biodistribution. Blood kinetic analysis revealed that EVs are rapidly cleared from the circulation with a half-life below 10 min. Our study demonstrates that radioactivity is the most accurate EV tracking approach for a complete quantitative biodistribution study including pharmacokinetic profiling. In conclusion, we provide a comprehensive comparison of fluorescent, bioluminescent, and radioactivity approaches, including dual labeling of EVs, to enable accurate spatiotemporal resolution of EV trafficking in mice, an essential step in developing EV therapeutics.
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http://dx.doi.org/10.1021/acsnano.0c09873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905875PMC
February 2021

Occurrence of Antibiotics, Antibiotic Resistance Genes and Viral Genomes in Wastewater Effluents and Their Treatment by a Pilot Scale Nanofiltration Unit.

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

iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal.

Broad-spectrum fluoroquinolone antibiotics (ciprofloxacin and levofloxacin), carbapenem and fluoroquinolone resistance genes, as well as viral genomes, were detected in grab samples of wastewater effluents. Passive samplers, which are simpler and easier to use and provide information about the concentrations and combination of contaminants present in a certain fluid matrix over time, proved to be extremely promising devices to monitor the presence of the target antibiotics in wastewater effluents. Nanofiltration was tested with a pilot-scale unit installed at a domestic wastewater treatment facility, using a Desal 5DK membrane operated at a constant transmembrane pressure of 6 bar and 70% recovery rate. In a 24 h experimental assay, the variation of the membrane permeance was low (6.3%). High rejections of the target contaminants from the wastewater effluent were obtained by the pilot-scale treatment. Hence, nanofiltration using the Desal 5DK membrane is considered to be a promising treatment to cope with chemical and biological contaminants present in wastewater effluents.
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http://dx.doi.org/10.3390/membranes11010009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824572PMC
December 2020

Inclusion Complex of Resveratrol with γ-Cyclodextrin as a Functional Ingredient for Lemon Juices.

Foods 2020 Dec 23;10(1). Epub 2020 Dec 23.

LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.

Microencapsulated resveratrol (RSV) is a pertinent ingredient in functional foods to be used in the prevention and management of cardiovascular diseases. Gamma-cyclodextrin (γ-CD) was evaluated for its RSV inclusion ability. Inclusion procedures comprised mixing equal concentration of an aqueous solution of γ-CD with an ethanol solution of RSV and freeze-drying to obtain a solid material. Solid-state characterization by vibrational spectroscopy, thermogravimetry, and powder X-ray diffraction (PXRD) confirmed the formation of the γ-CD·RSV complex in a ratio of 1:1. PXRD suggested that cyclodextrin molecules in the complex are stacked in infinite channels holding the RSV inside, with a wide inter-channel space where 14 water molecules are retained. Fresh lemon juices supplemented with 0.625 mg/mL of RSV in its free (RSV-juice) or complexed (γ-CD·RSV-juice) form were stored along 28 days under dark and room temperature or at 4 °C. Initially, the RSV level in γ-CD·RSV-juice was about nine times higher than in RSV-juice (43.1% and 4.8%, respectively), suggesting that the RSV complexation promoted its solubility in the lemon juice, a fact that was still noticed after 28 days of storage. Moreover, regardless the fact that the antioxidant capacity was similar among the juices, the loss of antiradical ABTS capacity in γ-CD·RSV-juice was reduced compared to that of the RSV-juice. Overall, this study allowed concluding that γ-CD can serve as a carrier of RSV, promoting its solubility and eventually protecting its antioxidant stability in lemon juices for at least 28 days.
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http://dx.doi.org/10.3390/foods10010016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822441PMC
December 2020

Harmine and Piperlongumine Revert TRIB2-Mediated Drug Resistance.

Cancers (Basel) 2020 Dec 9;12(12). Epub 2020 Dec 9.

Instituto de Investigaciones Biomédicas "Alberto Sols" (CSIC-UAM), Arturo Duperier 4, 28029 Madrid, Spain.

Therapy resistance is responsible for most relapses in patients with cancer and is the major challenge to improving the clinical outcome. The pseudokinase Tribbles homologue 2 (TRIB2) has been characterized as an important driver of resistance to several anti-cancer drugs, including the dual ATP-competitive PI3K and mTOR inhibitor dactolisib (BEZ235). TRIB2 promotes AKT activity, leading to the inactivation of FOXO transcription factors, which are known to mediate the cell response to antitumor drugs. To characterize the downstream events of TRIB2 activity, we analyzed the gene expression profiles of isogenic cell lines with different TRIB2 statuses by RNA sequencing. Using a connectivity map-based computational approach, we identified drug-induced gene-expression profiles that invert the TRIB2-associated expression profile. In particular, the natural alkaloids harmine and piperlongumine not only produced inverse gene expression profiles but also synergistically increased BEZ235-induced cell toxicity. Importantly, both agents promote FOXO nuclear translocation without interfering with the nuclear export machinery and induce the transcription of FOXO target genes. Our results highlight the great potential of this approach for drug repurposing and suggest that harmine and piperlongumine or similar compounds might be useful in the clinic to overcome TRIB2-mediated therapy resistance in cancer patients.
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http://dx.doi.org/10.3390/cancers12123689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763856PMC
December 2020

Application of Hydroxytyrosol in the Functional Foods Field: From Ingredient to Dietary Supplements.

Antioxidants (Basel) 2020 Dec 8;9(12). Epub 2020 Dec 8.

LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.

Hydroxytyrosol (HT) is an amphipathic functional phenol found in the olive tree, both in its leaves and fruits, in free or bound forms, as well as in olive oil and by-products of olive oil manufacture. The European Food Safety Authority recommends regular consumption of HT due to its several beneficial effects on human health, which are closely associated to its antioxidant activity. These reasons make HT an excellent candidate for application as a functional ingredient in the design of novel food products. Patents already exist for methodologies of extraction, purification, and application of HT in supplements and food products. The present review discusses the impact of HT incorporation on food properties and its effects on consumers, based on relevant data related to the use of HT as a functional ingredient, both as a pure compound or in the form of HT-rich extracts, in various food products, namely in edible oils, beverages, bakery products, as well animal-based foods such as meat, fishery and dairy products.
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http://dx.doi.org/10.3390/antiox9121246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763879PMC
December 2020

Burnout among Portuguese healthcare workers during the COVID-19 pandemic.

BMC Public Health 2020 Dec 7;20(1):1885. Epub 2020 Dec 7.

School of Education of Polytechnic of Porto, Centre for Research and Innovation in Education (inED), Porto, Portugal.

Background: During COVID-19 pandemic, healthcare workers (HCWs) have had high workload and have been exposed to multiple psychosocial stressors. The aim of this study was to evaluate HCWs in terms of the relative contributions of socio-demographic and mental health variables on three burnout dimensions: personal, work-related, and client-related burnout.

Methods: A cross-sectional study was performed using an online questionnaire spread via social networks. A snowball technique supported by health care institutions and professional organizations was applied.

Results: A total of 2008 subjects completed the survey. Gender, parental status, marriage status, and salary reduction were found to be significant factors for personal burnout. Health problems and direct contact with infected people were significantly associated with more susceptibility to high personal and work-related burnout. Frontline working positions were associated with all three dimensions. Higher levels of stress and depression in HCWs were significantly associated with increased levels of all burnout dimensions. Higher levels of satisfaction with life and resilience were significantly associated with lower levels of all burnout dimensions.

Conclusions: All three burnout dimensions were associated with a specific set of covariates. Consideration of these three dimensions is important when designing future burnout prevention programs for HCWs.
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http://dx.doi.org/10.1186/s12889-020-09980-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720923PMC
December 2020

Soft matter science and the COVID-19 pandemic.

Soft Matter 2020 Sep;16(36):8310-8324

Edinburgh Complex Fluids Partnership (ECFP), SUPA and School of Physics & Astronomy, The University of Edinburgh, Peter Guthrie Tait Road, Edinburgh EH9 3FD, UK.

Much of the science underpinning the global response to the COVID-19 pandemic lies in the soft matter domain. Coronaviruses are composite particles with a core of nucleic acids complexed to proteins surrounded by a protein-studded lipid bilayer shell. A dominant route for transmission is via air-borne aerosols and droplets. Viral interaction with polymeric body fluids, particularly mucus, and cell membranes controls their infectivity, while their interaction with skin and artificial surfaces underpins cleaning and disinfection and the efficacy of masks and other personal protective equipment. The global response to COVID-19 has highlighted gaps in the soft matter knowledge base. We survey these gaps, especially as pertaining to the transmission of the disease, and suggest questions that can (and need to) be tackled, both in response to COVID-19 and to better prepare for future viral pandemics.
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http://dx.doi.org/10.1039/d0sm01223hDOI Listing
September 2020

Anti-inflammatory and antinociceptive activity profile of a new lead compound - LQFM219.

Int Immunopharmacol 2020 Nov 3;88:106893. Epub 2020 Sep 3.

Laboratório de Química Farmacêutica Medicinal (LQFM), Faculdade de Farmácia, Universidade Federal de Goiás, Goiânia, GO, Brazil. Electronic address:

LQFM219 is a molecule designed from celecoxibe (COX-2 inhibitor) and darbufelone (inhibitor of COX-2 and 5-LOX) lead compounds through a molecular hybridisation strategy. Therefore, this work aimed to investigate the antinociceptive and anti-inflammatory activities of this new hybrid compound. The acute oral systemic toxicity of LQFM219 was evaluated via the neutral red uptake assay. Acetic acid-induced abdominal writhing and CFA-induced mechanical hyperalgesia were performed to evaluate the antinociceptive activity, and the anti-oedematogenic activity was studied by CFA-induced paw oedema and croton oil-induced ear oedema. Moreover, the acute anti-inflammatory activity was determined by carrageenan-induced pleurisy. In addition, cell migration, myeloperoxidase enzyme activity, and TNF-α and IL-1β levels were determined in pleural exudate. Moreover, a redox assay was conducted using electroanalytical and DPPH methods. The results demonstrated that LQFM219 was classified as GHS category 4, and it showed better free radical scavenger activity compared to BHT. Besides, LQFM219 decreased the number of writhings induced by acetic acid and the response to the mechanical stimulus in the CFA-induced mechanical hyperalgesia test. Furthermore, LQFM219 reduced oedema formation, cell migration, and IL-1β and TNF-α levels in the pleural cavity and inhibited myeloperoxidase enzyme activity. Thus, our study provides that the new pyrazole derivative, LQFM219, demonstrated low toxicity, antinociceptive and anti-inflammatory potential in vitro and in vivo.
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http://dx.doi.org/10.1016/j.intimp.2020.106893DOI Listing
November 2020

Poly-Epsilon-Lysine Hydrogels with Dynamic Crosslinking Facilitates Cell Proliferation.

Materials (Basel) 2020 Sep 1;13(17). Epub 2020 Sep 1.

EaStCHEM School of Chemistry, The University of Edinburgh, Edinburgh EH9 3FJ, UK.

The extracellular matrix (ECM) is a three-dimensional network within which fundamental cell processes such as cell attachment, proliferation, and differentiation occur driven by its inherent biological and structural cues. Hydrogels have been used as biomaterials as they possess many of the ECM characteristics that control cellular processes. However, the permanent crosslinking often found in hydrogels fails to recapitulate the dynamic nature of the natural ECM. This not only hinders natural cellular migration but must also limit cellular expansion and growth. Moreover, there is an increased interest in the use of new biopolymers to create biomimetic materials that can be used for biomedical applications. Here we report on the natural polymer poly-ε-lysine in forming dynamic hydrogels via reversible imine bond formation, with cell attachment promoted by arginine-glycine-aspartic acid (RGD) incorporation. Together, the mechanical properties and cell behavior of the dynamic hydrogels with low poly-ε-lysine quantities indicated good cell viability and high metabolic activity.
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http://dx.doi.org/10.3390/ma13173851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504584PMC
September 2020

Influence of Microwave-Assisted Drying on Structural Integrity and Viability of Testicular Tissues from Adult and Prepubertal Domestic Cats.

Biopreserv Biobank 2020 Oct 11;18(5):415-424. Epub 2020 Aug 11.

Smithsonian Conservation Biology Institute, National Zoological Park, Washington, District of Columbia, USA.

Anhydrous preservation is a promising approach for storage of living biomaterials at nonfreezing temperatures. Using the domestic cat model, the objectives of this study were to characterize changes in histology, DNA integrity, and viability of testicular tissues from adult versus prepubertal individuals during microwave-assisted drying. Testes from each age group were cut into small pieces before reversible membrane permeabilization, exposure to trehalose, and microwave-assisted drying during different time periods. In Experiment 1, water content was monitored for up to 40 minutes of drying. Tissues from adult or prepubertal cats experienced similar decreases of water content during the first 10 minutes. Desiccation progressed slowly between 10 and 20 minutes and then remained stable. In Experiment 2, structural properties were explored at 5, 10, and 20 minutes of desiccation. Percentages of normal seminiferous tubules were lower after 20 minutes drying in adult (43%) than in prepubertal tissues (61%). At the same time point, the proportion of cell degeneration was higher in adult (53%) than prepubertal tissues (28%). Percentages of intact DNA in tissues remained above 85% regardless of the microwave time in both age groups. Lastly, adult and prepubertal tissues only lost 33% of viability in both age groups. Collective results demonstrated for the first time that normal morphology, incidence of degeneration, DNA integrity, and viability of testicular tissues remained at acceptable levels during microwave-assisted drying for 20 minutes. Overall, prepubertal testicular tissues appeared to be more resilient to microwave-assisted desiccations than adult tissues. Importantly, water loss in the presence of trehalose after 20 minutes of desiccation already is compatible with long-term storage of testicular tissues at temperatures above -20°C, which is one step closer to future storage at supra-zero temperatures.
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http://dx.doi.org/10.1089/bio.2020.0048DOI Listing
October 2020

Flow dynamics of vitreous humour during saccadic eye movements.

J Mech Behav Biomed Mater 2020 10 30;110:103860. Epub 2020 Jun 30.

James Weir Fluids Laboratory, Department of Mechanical and Aerospace Engineering, University of Strathclyde, Glasgow, G1 1XJ, UK.

In this work, we reveal the flow dynamics of Vitreous Humour (VH) gel and liquid phases during saccadic movements of the eye, considering the biofluids viscoelastic character as well as realistic eye chamber geometry and taking into account the saccade profile. We quantify the differences in the flow dynamics of VH gel and liquid phases using viscoelastic rheological models that are able to model the VH shear rheology, considering different amplitudes of saccadic movements (10, 20, 30 and 40). For this purpose, the computational fluid dynamics (CFD) open source software OpenFOAM® was used. The results portray a distinct flow behaviour for the VH gel and liquid phases, with inertial effects being more significant for the VH liquid phase. Moreover, the Wall Shear Stress (WSS) values produced by the VH gel phase are more than twice of those generated by the VH liquid phase. Results also show that for different amplitudes of eye movement both the velocity magnitude in the vitreous cavity and the shear stresses on the cavity walls rise with increasing saccadic movement displacement.
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http://dx.doi.org/10.1016/j.jmbbm.2020.103860DOI Listing
October 2020

Fibrinogen and magnesium combination biomaterials modulate macrophage phenotype, NF-kB signaling and crosstalk with mesenchymal stem/stromal cells.

Acta Biomater 2020 09 18;114:471-484. Epub 2020 Jul 18.

i3S - Instituto de Investigação e Inovação em Saúde, and INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal; Instituto Ciências Biomédicas Abel Salazar da Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, Porto 4050-313, Portugal. Electronic address:

Macrophage behavior upon biomaterial implantation conditions the inflammatory response and subsequent tissue repair. The hypothesis behind this work was that fibrinogen (Fg) and magnesium (Mg) biomaterials, used in combination (FgMg) could act synergistically to modulate macrophage activation, promoting a pro-regenerative phenotype. Materials were characterized by scanning electron microscopy, Fg and Mg degradation products were quantified by atomic absorption spectroscopy and ELISA. Whole blood immune cells and primary human monocyte-derived macrophages were exposed to the biomaterials extracts in unstimulated (M0) or pro-inflammatory LPS or LPS-IFNγ (M1) conditions. Macrophage phenotype was evaluated by flow cytometry, cytokines secreted by whole blood cells and macrophages were measured by ELISA, and signaling pathways were probed by Western blotting. The secretomes of macrophages preconditioned with biomaterials extracts were incubated with human mesenchymal stem/stromal cells (MSC) and their effect on osteogenic differentiation was evaluated via Alkaline Phosphatase (ALP) activity and alizarin red staining. Scaffolds of Fg, alone or in the FgMg combination, presented similar 3D porous architectures. Extracts from FgMg materials reduced LPS-induced TNF-α secretion by innate immune cells, and macrophage M1 polarization upon LPS-IFNγ stimulation, resulting in lower cell surface CD86 expression, lower NFκB p65 phosphorylation and reduced TNF-α secretion. Moreover, while biomaterial extracts per se did not enhance MSC osteogenic differentiation, macrophage secretome, particularly from cells exposed to FgMg extracts, increased MSC ALP activity and alizarin red staining, compared with extracts alone. These findings suggest that the combination of Fg and Mg synergistically influences macrophage pro-inflammatory activation and crosstalk with MSC. STATEMENT OF SIGNIFICANCE: Modulating macrophage phenotype by degradable and bioactive biomaterials is an increasingly explored strategy to promote tissue repair/regeneration. Fibrinogen (Fg) and magnesium (Mg)-based materials have been explored in this context. Previous work from our group showed that monocytes interact with fibrinogen adsorbed onto chitosan surfaces through TLR4 and that fibrinogen scaffolds promote in vivo bone regeneration. Also, magnesium ions have been reported to modulate macrophage pro-inflammatory M1 stimulation and to promote bone repair. Here we report, for the first time, the combination of Fg and Mg materials, hypothesizing that it could act synergistically on macrophages, directing them towards a pro-regenerative phenotype. As a first step towards proving/disproving our hypothesis we used extracts obtained from Fg, Mg and FgMg multilayer constructs. We observed that FgMg extracts led to a reduction in the polarization of macrophages towards a pro-inflammatory phenotype. Also, the secretome of macrophages exposed to extracts of the combination material promoted the expression of osteogenic markers by MSCs.
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http://dx.doi.org/10.1016/j.actbio.2020.07.028DOI Listing
September 2020

Clearance and persistence of SARS-CoV-2 RNA in patients with COVID-19.

J Med Virol 2020 10 19;92(10):2227-2231. Epub 2020 Jun 19.

Laboratory of Molecular Biology/Virology, Clinical Pathology Unit, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

Patients with coronavirus disease-2019 may be discharged based on clinical resolution of symptoms, and evidence for viral RNA clearance from the upper respiratory tract. Understanding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral clearance profile is crucial to establish a re-testing plan on discharge and ending isolation of patients. We aimed to evaluate the number of days that a patient needed to achieve undetectable levels of SARS-CoV-2 in upper respiratory tract specimens (nasopharyngeal swab and/or an oropharyngeal swab). The clearance and persistence of viral RNA was evaluated in two groups of positive patients: those who achieved two negative reverse transcription-polymerase chain reaction (RT-PCR) tests and those who kept testing positive. Patients were organized thereafter in two subgroups, mild illness patients discharged home and inpatients who had moderate to severe illness. Results from RT-PCR tests were then correlated with results from the evaluation of the immune response. The study evidenced that most patients tested positive for more than 2 weeks and that persistence of viral RNA is not necessarily associated with severe disease but may result from a weaker immune response instead.
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http://dx.doi.org/10.1002/jmv.26103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301002PMC
October 2020

Green Microalgae Utilization for the Adsorptive Removal of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) from Water Samples.

Int J Environ Res Public Health 2020 05 25;17(10). Epub 2020 May 25.

Department of Environment and Planning, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.

In view of the valorisation of the green microalga biomass, it was used for the biosorption of two nonsteroidal anti-inflammatory drugs, namely salicylic acid and ibuprofen, from water. Microalgae biomass was characterized, namely by the determination of the point of zero charge (pH), by Fourier transform infrared (FT-IR) analysis, simultaneous thermal analysis (STA) and scanning electron microscopy with energy dispersive spectroscopy (SEM/EDS). Kinetic and equilibrium batch experiments were carried out and results were found to fit the pseudo-second order equation and the Langmuir isotherm model, respectively. The Langmuir maximum capacity determined for salicylic acid (63 mg g) was larger than for ibuprofen (12 mg g), which was also verified for a commercial activated carbon used as reference (with capacities of 250 and 147 mg g, respectively). For both pharmaceuticals, the determination of thermodynamic parameters allowed us to infer that adsorption onto microalgae biomass was spontaneous, favourable and exothermic. Furthermore, based on the biomass characterization after adsorption and energy associated with the process, it was deduced that the removal of salicylic acid and ibuprofen by biomass occurred by physical interaction.
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http://dx.doi.org/10.3390/ijerph17103707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277159PMC
May 2020

Pyromellitic dianhydride crosslinked soluble cyclodextrin polymers: Synthesis, lopinavir release from sub-micron sized particles and anti-HIV-1 activity.

Int J Pharm 2020 Jun 20;583:119356. Epub 2020 Apr 20.

Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal. Electronic address:

We report the synthesis of water soluble cyclodextrin (CD) polymers prepared by crosslinking pyromellitic dianhydride (PMDA) with two CD derivatives (methyl-β-CD - MβCD and (2-hydroxy)propyl-β-CD - HPβCD) and their evaluation as functional sub-micron sized carriers in the development of antiretroviral drug delivery systems. Using the protease inhibitor lopinavir (LPV) as model drug, LPV loaded CD polymers (pHPβCD and pMβCD) were prepared and fully characterized. The physicochemical characterization and in vitro drug release confirmed the successful synthesis of pHPβCD and pMβCD, the formation of sub-micron sized particles and a 12-14 fold increase in LPV solubility. Cytotoxicity assays indicated that both pHPβCD and pMβCD were able to improve the safety profile of LPV while the viral infectivity assay revealed a concentration independent anti-HIV-1 effect for both pHPβCD and pMβCD with a maximum percentage inhibition (MPI) of 79 and 91% respectively. After LPV loading, the antiviral profile of pHPβCD was reversed to the sigmoidal dose-response profile of LPV, while pMβCD maintained its dose-independent profile followed by a LPV mediated increase in viral inhibition. Overall, both pHPβCD and pMβCD demonstrated anti-HIV-1 activity, while drug loaded pMβCD indicated its potential as functional sub-micron sized drug delivery polymers for achieving synergistic anti-HIV activity.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119356DOI Listing
June 2020

Association of the polymorphisms of the genes APOC3 (rs2854116), ESR2 (rs3020450), HFE (rs1799945), MMP1 (rs1799750) and PPARG (rs1801282) with lipodystrophy in people living with HIV on antiretroviral therapy: a systematic review.

Mol Biol Rep 2020 Jun 22;47(6):4779-4787. Epub 2020 Apr 22.

Faculdade de Ciências Médicas (FCM), Universidade de Pernambuco (UPE), Recife, PE, Brazil.

The aim of this study was to perform a systematic review to identify data reported in the literature concerning the association of APOC3 (rs2854116), ESR2 (rs3020450), HFE (rs1799945), MMP1 (rs1799750) and PPARG (rs1801282) polymorphisms with lipodystrophy in people living with HIV (PLWHIV) on antirretroviral therapy. The research was conducted in six databases and the studies were selected in two steps. First, a search was undertaken in the following electronic databases: PubMed, Science Direct, Medline, World Wide Science, Directory of Open Access Journals, Scielo, Lilacs and Medcarib. The titles and abstracts of 24,859 articles were read to select those that match the elegibilty criteria. Five papers that addressed the association of HAART, lipodystrophy and polymorphisms were selected for the review. There was no association between the polymorphisms of the genes APOC3 and PPARG and lipodystrophy. Another study described an association between the variant allele (G) of HFE and protection concerning the development of lipoatrophy (0.02) when compared with the reference allele (C). On the other hand, the variant allele (T) of the ESR2 gene was associated with the development of lipoatrophy (p = 0.007) when compared with the reference allele (C). In addition, the genotype and the variant allele of the gene MMP1 (2G) were associated with lipodystrophy in PLWHIV on HAART (p = 0.0002 and p = 0.0008, respectively). Therefore, further studies with other populations, involving PLWHIV on HAART are necessary to better understand the role of genetic markers, which may be involved in a predisposition to lipodystrophy.
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http://dx.doi.org/10.1007/s11033-020-05441-3DOI Listing
June 2020