Publications by authors named "Sara Silva"

147 Publications

Kingella kingae: An Unlikely Cause of Meningitis.

Pediatr Infect Dis J 2021 Mar 2. Epub 2021 Mar 2.

From the Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, EPE Pediatrics Department, Hospital da Criança e do Adolescente, Hospital da Luz Lisboa CHRC, CEDOC, Chronic Diseases Research Center, NOVA Medical School Clinical Pathology Laboratory (Synlab), Hospital da Luz Lisboa CEDOC, Chronic Diseases Research Center, NOVA Medical School Clinical Microbiology, Laboratório SYNLAB, Lisboa, Portugal.

Kingella kingae is the leading cause of osteoarticular infections between 6 and 48 months, a well-known cause of pediatric bacteremia and endocarditis and has been rarely associated with meningitis. We report a case of a healthy 10-year-old boy with meningitis due to Kingella kingae who presented with a history of severe headache, vomiting and prostration.
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http://dx.doi.org/10.1097/INF.0000000000003112DOI Listing
March 2021

Individual and contextual predictors of children's hemoglobin levels from Southern Brazilian municipalities in social vulnerability.

Cad Saude Publica 2021 11;36(12):e00166619. Epub 2021 Jan 11.

Departamento de Nutrição, Universidade Federal do Paraná, Curitiba, Brasil.

Few studies have investigated the simultaneous effect of individual and contextual factors on the occurrences of anemia. This study aims to evaluate the variability of children's hemoglobin levels from municipalities in social vulnerability and its association with factors of individual and municipal nature. This is a cross-sectional, multi-center study, with children data (12-59 months) collected from 48 municipalities of the Southern region of Brazil, that were included in the Brazil Without Poverty Plan. Individuals' data were collected using a structured questionnaire, and secondary and ecological data of children's municipalities were collected via national surveys and institutional websites. The outcome was defined as the hemoglobin level obtained by HemoCue. A multilevel analysis was performed using Generalized Linear Models for Location Scale and Shape using R, with a 5% significance level. A total of 1,501 children were evaluated. The mean hemoglobin level was 12.8g/dL (95%CI: 12.7-12.8), with significant variability between municipalities. Lower values of hemoglobin were observed in children who lived in municipalities with a higher urbanization rate and a lower number of Community Health Agents, in relation to the reference categories. At the individual level, lower hemoglobin values were identified for children under 24 months, not enrolled at daycares, who were beneficiaries of the conditional cash transfer program and diagnosed with underweight. The results shed light on important factors at the municipal and the individual levels that were associated to the hemoglobin levels of children living in municipalities in social vulnerability.
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http://dx.doi.org/10.1590/0102-311X00166619DOI Listing
January 2021

Model Amphipathic Peptide Coupled with Tacrine to Improve Its Antiproliferative Activity.

Int J Mol Sci 2020 Dec 29;22(1). Epub 2020 Dec 29.

OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Plácido da Costa, 4200-450 Porto, Portugal.

Drug repurposing and drug combination are two strategies that have been widely used to overcome the traditional development of new anticancer drugs. Several FDA-approved drugs for other indications have been tested and have demonstrated beneficial anticancer effects. In this connection, our research group recently reported that Tacrine, used to treat Alzheimer's Disease, inhibits the growth of breast cancer MCF-7 cells both alone and in combination with a reference drug. In this view, we have now coupled Tacrine with the model amphipathic cell-penetrating peptide (CPP) MAP, to ascertain whether coupling of the CPP might enhance the drug's antiproliferative properties. To this end, we synthesized MAP through solid-phase peptide synthesis, coupled it with Tacrine, and made a comparative evaluation of the parent drug, peptide, and the conjugate regarding their permeability across the blood-brain barrier (BBB), ability to inhibit acetylcholinesterase (AChE) in vitro, and antiproliferative activity on cancer cells. Both MAP and its Tacrine conjugate were highly toxic to MCF-7 and SH-SY5Y cells. In turn, BBB-permeability studies were inconclusive, and conjugation to the CPP led to a considerable loss of Tacrine function as an AChE inhibitor. Nonetheless, this work reinforces the potential of repurposing Tacrine for cancer and enhances the antiproliferative activity of this drug through its conjugation to a CPP.
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http://dx.doi.org/10.3390/ijms22010242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795729PMC
December 2020

Salivary immunoglobulins (A, G, and M) in type 1 diabetes mellitus patients: A PROSPERO-registered systematic review and meta-analysis.

Arch Oral Biol 2021 Feb 8;122:105025. Epub 2020 Dec 8.

Department of Clinical Dentistry, School of Dentistry, Federal University of Ceará, Rua Monsenhor Furtado, s/n, Rodolfo Teófilo, CEP: 60430-160, Fortaleza, Ceará, Brazil. Electronic address:

Objective: To assess the difference in the salivary levels of immunoglobulins between patients with type 1 diabetes mellitus (DM1) and healthy controls.

Design: This systematic review was registered on the PROSPERO (CRD42020159198) database. All references were cross-checked and the risk of bias assessment was conducted using the Newcastle-Ottawa Scale. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to appraise the quality of evidence. The standardized mean difference and Cohen's d as the effect size were used in the meta-analysis. I-square statistics was used to estimate heterogeneity. Analysis was performed using the RevMan® software (p < 0.05) with a 95 % confidence interval.

Results: Of the total 92 articles, 9 were selected for this study. The meta-analysis included 333 DM1 patients and 325 healthy controls. DM1 patients showed a significant reduction in salivary flow (p = 0.0008; Cohen's d= -0.19, CI 95 %= -0.33, -0.05), although not significant enough to modify the IgA concentration (p = 0.120; Cohen's d = 0.58, CI 95 %= -0.15, 1.32). However, DM1 increased IgA concentration by reducing salivary flow (Cohen's d = 0.84; CI 95 % = 0.36, 1.32), with a strong estimate of effect (p = 0.0006). Regarding IgG, no significant change was noted with DM1 in the patient's saliva (p = 0.420). Furthermore, there was no significant variation in the salivary IgM levels (p = 0.300).

Conclusions: The data suggest that the salivary levels of the evaluated immunoglobulins do not seem to be altered in DM1 patients when compared to that in healthy controls. However, the increase in IgA salivary concentration was dependent on total protein estimation.
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http://dx.doi.org/10.1016/j.archoralbio.2020.105025DOI Listing
February 2021

Potential prebiotic effect of fruit and vegetable byproducts flour using in vitro gastrointestinal digestion.

Food Res Int 2020 11 4;137:109354. Epub 2020 Jun 4.

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:

Fruit and vegetable byproducts (FVBP) present high content of bioactive compounds and dietary fibers and have demonstrated a positive modulatory effect upon gut microbiota composition. In the present study, the prebiotic potential of a FVBP flour obtained from solid byproducts after fruit and vegetable processing was evaluated after in vitro gastrointestinal digestion. An initial screening with three strains of Lactobacillus (Lactobacillus casei 01, Lactobacillus rhamnosus R11 and Lactobacillus acidophilus LA-5®) and one Bifidobacterium strain (Bifidobacterium animalis spp. lactis BB12®) was carried out and then the prebiotic effect of FVBP flour was performed with fecal samples of five donors. The changes in gut microbiota were evaluated at 0, 12, 24 and 48 h of fermentation by the real-time polymerase chain reaction (qPCR) method with 16S rRNA-based specific primers. The pH and short chain fatty acids (SCFA) production at each fermentation time were assessed. The fructooligosaccharides (FOS) were used as positive control. The impact of FVBP flour upon cell viability was also evaluated. FVBP flour showed higher prebiotic effect than FOS on growth enhancement of Lactobacillus after 48 h of fermentation and similar bifidogenic effect as FOS on Bifidobacterium growth at 12, 24 and 48 h of fermentation. SCFA production was observed when FVBP flour was used as carbon source, including butyrate, which supports the prebiotic potential of this flour. Additionally, it was observed that after in vitro gastrointestinal digestion, the FVBP flour at 3% promoted cell metabolism of Caco-2 cell line up to 67%. Thus, the present study demonstrates the viability of using a fruit and vegetable byproducts flour as a potential sustainable prebiotic source.
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http://dx.doi.org/10.1016/j.foodres.2020.109354DOI Listing
November 2020

Blueberry Consumption Challenges Hepatic Mitochondrial Bioenergetics and Elicits Transcriptomics Reprogramming in Healthy Wistar Rats.

Pharmaceutics 2020 Nov 14;12(11). Epub 2020 Nov 14.

Institute of Pharmacology & Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.

An emergent trend of blueberries' (BB) "prophylactic" consumption, due to their phytochemicals' richness and well-known health-promoting claims, is widely scaled-up. However, the benefits arising from BB indiscriminate intake remains puzzling based on incongruent preclinical and human data. To provide a more in-depth elucidation and support towards a healthier and safer consumption, we conducted a translation-minded experimental study in healthy Wistar rats that consumed BB in a juice form (25 g/kg body weight (BW)/day; 14 weeks' protocol). Particular attention was paid to the physiological adaptations succeeding in the gut and liver tissues regarding the acknowledged BB-induced metabolic benefits. Systemically, BB boosted serum antioxidant activity and repressed the circulating levels of 3-hydroxybutyrate (3-HB) ketone bodies and 3-HB/acetoacetate ratio. Moreover, BB elicited increased fecal succinic acid levels without major changes on gut microbiota (GM) composition and gut ultra-structural organization. Remarkably, an accentuated hepatic mitochondrial bioenergetic challenge, ensuing metabolic transcriptomic reprogramming along with a concerted anti-inflammatory pre-conditioning, was clearly detected upon long-term consumption of BB phytochemicals. Altogether, the results disclosed herein portray a quiescent mitochondrial-related metabolomics and hint for a unified adaptive response to this nutritional challenge. The beneficial or noxious consequences arising from this dietary trend should be carefully interpreted and necessarily claims future research.
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http://dx.doi.org/10.3390/pharmaceutics12111094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697217PMC
November 2020

Multitask ATPases (NBDs) of bacterial ABC importers type I and their interspecies exchangeability.

Sci Rep 2020 11 11;10(1):19564. Epub 2020 Nov 11.

Microbial Genetics Laboratory, UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências E Tecnologia, Universidade NOVA de Lisboa, Quinta da Torre, 2829-516, Caparica, Portugal.

ATP-binding cassette (ABC) type I importers are widespread in bacteria and play a crucial role in its survival and pathogenesis. They share the same modular architecture comprising two intracellular nucleotide-binding domains (NBDs), two transmembrane domains (TMDs) and a substrate-binding protein. The NBDs bind and hydrolyze ATP, thereby generating conformational changes that are coupled to the TMDs and lead to substrate translocation. A group of multitask NBDs that are able to serve as the cellular motor for multiple sugar importers was recently discovered. To understand why some ABC importers share energy-coupling components, we used the MsmX ATPase from Bacillus subtilis as a model for biological and structural studies. Here we report the first examples of functional hybrid interspecies ABC type I importers in which the NBDs could be exchanged. Furthermore, the first crystal structure of an assigned multitask NBD provides a framework to understand the molecular basis of the broader specificity of interaction with the TMDs.
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http://dx.doi.org/10.1038/s41598-020-76444-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658222PMC
November 2020

Textile dyes loaded chitosan nanoparticles: Characterization, biocompatibility and staining capacity.

Carbohydr Polym 2021 Jan 22;251:117120. Epub 2020 Sep 22.

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

Textile dyeing is a hazardous and toxic process. While traditionally it has been managed through effluent treatment, new approaches focused upon improving the dyeing process are gaining relevance. In this work, we sought to obtain, for the first time, an eco-friendly chitosan-nanoparticle based textile dyeing method. To that end, yellow everzol and navy blue itosperse loaded chitosan nanoparticles were produced and their capacity to dye textiles and cytotoxicity towards human skin cells were evaluated. The results obtained showed that it was possible to obtain nanoencapsulated dyes through ionic gelation with an average entrapment efficacy above 90 %. Nanoparticles presented a positive surface charge and sizes between 190 and 800 nm with yellow everzol NPs occurring via ionic interactions while navy blue itosperse NPs were formed through hydrogen bonds. Furthermore, the produced dye NPs presented no cytotoxicity towards HaCat cells and presented staining percentages reaching 17.60 % for a viscose/wool blend.
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http://dx.doi.org/10.1016/j.carbpol.2020.117120DOI Listing
January 2021

Formulation, Characterization and Evaluation against SH-SY5Y Cells of New Tacrine and Tacrine-MAP Loaded with Lipid Nanoparticles.

Nanomaterials (Basel) 2020 Oct 21;10(10). Epub 2020 Oct 21.

OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Plácido da Costa, 4200-450 Porto, Portugal.

Tacrine (TAC) was the first FDA approved drug for the treatment of Alzheimer's disease, resulting in increased memory and enhanced cognitive symptoms in patients. However, long-term therapy presents poor patient compliance associated with undesired side effects such as nausea, vomiting and hepatoxicity. To improve its therapeutic efficacy and decrease toxicity, the use of nanoparticles could be applied as a possible solution to delivery TAC. In this context, a project has been designed to develop a new nanostructured lipid carrier (NLC) as a delivery system for TAC and conjugate TAC and model amphipathic peptide (MAP) to decrease TAC limitations. Different formulations loaded with TAC and TAC + MAP were prepared using a combination of Compritol 888 ATO as the solid lipid and Transcutol HP as the liquid lipid component. Physical characterization was evaluated in terms of particle size, surface charge, encapsulation efficiency and in vitro drug release studies. Particle size distributions within the nanometer range were obtained with encapsulation efficiencies of 72.4% for the TAC and 85.6% for the TAC + MAP conjugate. Furthermore, cytotoxicity of all NLC formulations was determined against neuroblastoma cell line SH-SY5Y. The optimized TAC delivery system revealed low toxicity suggesting this could be a potential carrier system to deliver TAC. However, TAC + MAP conjugated even encapsulated in the NLC system demonstrated toxicity against the SH-SY5Y cell line.
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http://dx.doi.org/10.3390/nano10102089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589787PMC
October 2020

Cell-penetrating peptides in oncologic pharmacotherapy: A review.

Pharmacol Res 2020 12 4;162:105231. Epub 2020 Oct 4.

OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Porto, Portugal; Faculty of Pharmacy, University of Porto, Porto, Portugal.

Cancer is the second leading cause of death in the world and its treatment is extremely challenging, mainly due to its complexity. Cell-Penetrating Peptides (CPPs) are peptides that can transport into the cell a wide variety of biologically active conjugates (or cargoes), and are, therefore, promising in the treatment and in the diagnosis of several types of cancer. Some notable examples are TAT and Penetratin, capable of penetrating the central nervous system (CNS) and, therefore, acting in cancers of this system, such as Glioblastoma Multiforme (GBM). These above-mentioned peptides, conjugated with traditional chemotherapeutic such as Doxorubicin (DOX) and Paclitaxel (PTX), have also been shown to induce apoptosis of breast and liver cancer cells, as well as in lung cancer cells, respectively. In other cancers, such as esophageal cancer, the attachment of Magainin 2 (MG2) to Bombesin (MG2B), another CPP, led to pronounced anticancer effects. Other examples are CopA3, that selectively decreased the viability of gastric cancer cells, and the CPP p28. Furthermore, in preclinical tests, the anti-tumor efficacy of this peptide was evaluated on human breast cancer, prostate cancer, ovarian cancer, and melanoma cells in vitro, leading to high expression of p53 and promoting cell cycle arrest. Despite the numerous in vitro and in vivo studies with promising results, and the increasing number of clinical trials using CPPs, few treatments reach the expected clinical efficacy. Usually, their clinical application is limited by its poor aqueous solubility, immunogenicity issues and dose-limiting toxicity. This review describes the most recent advances and innovations in the use of CPPs in several types of cancer, highlighting their crucial importance for various purposes, from therapeutic to diagnosis. Further clinical trials with these peptides are warranted to examine its effects on various types of cancer.
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http://dx.doi.org/10.1016/j.phrs.2020.105231DOI Listing
December 2020

Bioactive extracts from brewer's spent grain.

Food Funct 2020 Oct;11(10):8963-8977

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

In this study, antioxidant-rich extracts from brewer's spent grain (BSG) extracted by solid-to-liquid extraction using different solvents water and ethanol and their mixtures at two ratios (80% ethanol : water (v/v) and 60% ethanol : water (v/v)) were characterized. Nutritional composition was evaluated for the extracts and for the solid residues obtained after extraction. Additionally, the extracts were analyzed for the total phenolic content and individual phenolic compounds and related biological properties including antioxidant capacity (ABTS; ORAC and DNA protection), antihypertensive capacity, antibacterial activity and antibiofilm capacity. Safety was also demonstrated through genotoxicity and cytotoxicity tests. The results obtained showed that while all the extracts exhibited high antioxidant capacity (except ethanolic extract), the highest values were obtained for the 60% ethanol : water extract. The identification of phenolic compounds using HPLC showed that catechin and vanillin were the main compounds identified with the highest concentration being obtained for 60% ethanol : water extraction. In the biological activity assays, water and hydroethanolic extracts were multifunctional (antioxidant and antihypertensive capacity, antibacterial and antibiofilm activity), and the 80% ethanol : water presented better results in some assays. All were non-genotoxic, but the cytotoxicity was dependent on the extract concentration, with complete safe application for all up to 1 mg mL-1. Therefore, this study shows the potential of a viable green solvent based and low cost extraction recovery method of bioactive compounds from brewer's spent grain.
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http://dx.doi.org/10.1039/d0fo01426eDOI Listing
October 2020

Hydrogen-bonded host-guest systems are stable in ionic liquids.

Sci Rep 2020 Sep 22;10(1):15414. Epub 2020 Sep 22.

IMDEA Nanociencia, Faraday 9, Campus UAM, 28049, Madrid, Spain.

We show that H-bonded host-guest systems associate in ionic liquids (ILs), pure salts with melting point below room temperature, in which dipole-dipole electrostatic interactions should be negligible in comparison with dipole-charge interactions. Binding constants (K) obtained from titrations of four H-bonded host-guest systems in two organic solvents and two ionic liquids yield smaller yet comparable K values in ionic liquids than in organic solvents. We also detect the association event using force spectroscopy, which confirms that the binding is not solely due to (de)solvation processes. Our results indicate that classic H-bonded host-guest supramolecular chemistry takes place in ILs. This implies that strong H-bonds are only moderately affected by surroundings composed entirely of charges, which can be interpreted as an indication that the balance of Coulombic to covalent forces in strong H-bonds is not tipped towards the former.
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http://dx.doi.org/10.1038/s41598-020-71803-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508985PMC
September 2020

Are olive pomace powders a safe source of bioactives and nutrients?

J Sci Food Agric 2020 Sep 10. Epub 2020 Sep 10.

CBQF - Centro de Biotecnologia e Química Fina, Laboratório Associado, Universidade Católica Portuguesa, Escola Superior de Biotecnologia, Porto, Portugal.

Background: The olive oil industry generates significant amounts of semi-solid wastes, namely olive pomace. Olive pomace is a by-product rich in high-value compounds (e.g. dietary fibre, unsaturated fatty acids, polyphenols) widely explored to obtain new food ingredients. However, conventional extraction methods frequently use organic solvents, while novel eco-friendly techniques have high operational costs. The development of powdered products without any extraction step has been proposed as a more feasible and sustainable approach.

Results: The present study fractionated and valorized the liquid and pulp fraction of olive pomace obtaining two stable and safe powdered ingredients, namely a liquid-enriched powder (LOPP) and a pulp-enriched powder (POPP). These powders were characterized chemically, and their bioactivity was assessed. LOPP exhibited a significant amount of mannitol (141 g kg ), potassium (54 g kg ) and hydroxytyrosol derivatives (5 mg g ). POPP exhibited a high amount of dietary fibre (620 g kg ) associated with a significant amount of bound phenolics (7.41 mg GAE g fibre DW) with substantial antioxidant activity. POPP also contained an unsaturated fatty acid composition similar to that of olive oil (76% of total fatty acids) and showed potential as a reasonable source of protein (12%). Their functional properties (solubility, water-holding and oil-holding capacity), antioxidant capacity and antimicrobial activity were also assessed, and their biological safety was verified.

Conclusions: The development of olive pomace powders for application in the food industry could be a suitable strategy to add value to olive pomace and obtain safe multifunctional ingredients with higher health-promoting effects than dietary fibre and polyphenols. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.10812DOI Listing
September 2020

Effect of High Hydrostatic Pressure Extraction on Biological Activities and Phenolics Composition of Winter Savory Leaf Extracts.

Antioxidants (Basel) 2020 Sep 8;9(9). Epub 2020 Sep 8.

CBQF-Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa, 4169-005 Porto, Portugal.

L. has several biological properties related to its diverse composition of secondary metabolites. Nevertheless, it has been mainly studied for its essential oil, with only a few studies on the profile and bioactivities of the bioactive compounds from its leaf extracts being reported. This work aimed to study the antioxidant activity (by oxygen radical absorbance capacity (ORAC) assay), antimicrobial minimum inhibitory and bactericidal concentrations (MIC and MBC) determination, antibiofilm (by colorimetry), impact upon DNA (anti- and pro-oxidant assay), and cytotoxicity (by cell metabolism viability assays) of extracts obtained by high-pressure-assisted extraction (HPE). The extract obtained at 348 MPa, 35% (/) ethanol presented the highest concentration of individual phenolic compounds, and a minimum bactericidal concentration of 20 mg/mL against . HPE extracts showed antioxidant activity not only in ORAC but they were also able to prevent/attenuate peroxide-induced damage upon DNA. Moreover, on its own, HPE extract induced less oxidative damage than the control extract. Concerning the cytotoxicity, HPE extracts (at 0.5 and 1.0 mg/mL) were not harmful to HT29 cell lines, while control extracts (obtained at atmospheric pressure) at higher concentrations (>1.0 mg/mL) slightly reduced the metabolism of the cells. Finally, all extracts showed inhibition of the viability of 3 cancerous cell lines (>2.0 mg/mL for Caco-2, HeLa, and TR146) to below 15%.
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http://dx.doi.org/10.3390/antiox9090841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554779PMC
September 2020

The Dysfunctional Immune System in Common Variable Immunodeficiency Increases the Susceptibility to Gastric Cancer.

Cells 2020 06 19;9(6). Epub 2020 Jun 19.

Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.

Gastric carcinoma (GC) represents the most common cause of death in patients with common variable immunodeficiency (CVID). However, a limited number of cases have been characterised so far. In this study, we analysed the clinical features, bacterial/viral infections, detailed morphology and immune microenvironment of nine CVID patients with GC. The study of the immune microenvironment included automated digital counts of CD20+, CD4+, CD8+, FOXP3+, GATA3+ and CD138+ immune cells, as well as the evaluation of PD-L1 expression. Twenty-one GCs from non-CVID patients were used as a control group. GC in CVID patients was diagnosed mostly at early-stage ( = 6/9; 66.7%) and at younger age (median-age: 43y), when compared to non-CVID patients ( < 0.001). GC pathogenesis was closely related to infection ( = 8/9; 88.9%), but not to Epstein-Barr virus (0.0%) or cytomegalovirus infection (0.0%). Non-neoplastic mucosa (non-NM) in CVID-patients displayed prominent lymphocytic gastritis (100%) and a dysfunctional immune microenvironment, characterised by higher rates of CD4+/CD8+/Foxp3+/GATA3+/PD-L1+ immune cells and the expected paucity of CD20+ B-lymphocytes and CD138+ plasma cells, when compared to non-CVID patients ( < 0.05). Changes in the immune microenvironment between non-NM and GC were not equivalent in CVID and non-CVID patients, reflecting the relevance of immune dysfunction for gastric carcinogenesis and GC progression in the CVID population.
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http://dx.doi.org/10.3390/cells9061498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349552PMC
June 2020

Characterization of β-cyclodextrin/myrtenol complex and its protective effect against nociceptive behavior and cognitive impairment in a chronic musculoskeletal pain model.

Carbohydr Polym 2020 Sep 30;244:116448. Epub 2020 May 30.

Department of Physiology, Federal University of Sergipe, São Cristóvão, SE, Brazil.

Myrtenol has gained wide interest because of its pharmacological profiles, mainly for treatment of chronic diseases. To improve the solubility of myrtenol, the formation of inclusion complexes with β-cyclodextrin was performed by physical mixture, kneading process or slurry complexation (SC) methods and characterized using thermal analysis, XRD, SEM and NMR. From these results, myrtenol complexed by SC was successfully complexed into β-cyclodextrin cavity. The interaction between myrtenol and β-cyclodextrin was confirmed by molecular docking. Hence, the SC β-cyclodextrin-myrtenol complex was evaluate for its anti-hyperalgesic, anxiolytic and antioxidant activity in a fibromyalgia model. Results show that myrtenol and β-cyclodextrin form a stable complex and have anti-hyperalgesic effect, improve the cognitive impairment caused and have an anxiolytic-like effect. Furthermore, the β-cyclodextrin/myrtenol complex decrease lipoperoxidation, increased catalase activity and a reduce SOD/CAT ratio. Therefore, β-cyclodextrin/myrtenol complex reduce painful behavior, improves motor skills and emotional behavior and decreases oxidative stress in a fibromyalgia model.
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http://dx.doi.org/10.1016/j.carbpol.2020.116448DOI Listing
September 2020

Clinical signs, MRI findings and outcome in dogs with peripheral vestibular disease: a retrospective study.

BMC Vet Res 2020 May 25;16(1):159. Epub 2020 May 25.

Department of Small Animal Clinical Science, Institute of Veterinary Science, University of Liverpool, Neston, CH64 7TE, UK.

Background: Vestibular dysfunction is relatively common in dogs, with a prevalence of 0.08% reported in primary veterinary care in the UK. There are several studies investigating how to differentiate between peripheral and central vestibular disease but only limited information regarding the possible underlying causes for peripheral vestibular dysfunction in dogs. This study therefore aimed to describe the clinical signs, magnetic resonance imaging findings (MRI), underlying causes and outcome in a large population of dogs diagnosed with peripheral vestibular disease.

Results: One hundred eighty-eight patients were included in the study with a median age of 6.9 years (range 3 months to 14.6 years). Neurological abnormalities included head tilt (n = 185), ataxia (n = 123), facial paralysis (n = 103), nystagmus (n = 97), positional strabismus (n = 93) and Horner syndrome (n = 7). The most prevalent diagnosis was idiopathic vestibular disease (n = 128), followed by otitis media and/or interna (n = 49), hypothyroidism (n = 7), suspected congenital vestibular disease (n = 2), neoplasia (n = 1) and cholesteatoma (n = 1). Long-term follow-up revealed persistence of head tilt (n = 50), facial paresis (n = 41) and ataxia (n = 6) in some cases. Recurrence of clinical signs was observed in 26 dogs. Increasing age was associated with a mild increased chance of diagnosis of idiopathic vestibular syndrome rather than otitis media and/or interna (P = 0.022, OR = 0.866; CI 0.765-0.980). History of previous vestibular episodes (P = 0.017, OR = 3.533; CI 1.251-9.981) was associated with an increased likelihood of resolution of the clinical signs whilst contrast enhancement of cranial nerves VII and/or VIII on MRI (P = 0.018, OR = 0.432; CI 0.251-0.868) was associated with a decreased chance of resolution of the clinical signs.

Conclusions: Idiopathic vestibular disease is the most common cause of peripheral vestibular dysfunction in dogs and it is associated with advanced age. Incomplete recovery from peripheral vestibular disease is common, especially in dogs presenting with cranial nerve enhancement on MRI but less so if there is previous history of vestibular episodes.
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http://dx.doi.org/10.1186/s12917-020-02366-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249679PMC
May 2020

[Feeding and nutrition efforts in the context of primary healthcare in BrazilMedidas relativas a la alimentación y la nutrición en la atención primaria de salud en Brasil].

Rev Panam Salud Publica 2020 23;44:e39. Epub 2020 Apr 23.

Ministério da Saúde, Secretaria de Atenção Primária à Saúde Departamento de Promoção da Saúde Coordenação-Geral de Alimentação e Nutrição Brasília (DF) Brasil Ministério da Saúde, Secretaria de Atenção Primária à Saúde, Departamento de Promoção da Saúde, Coordenação-Geral de Alimentação e Nutrição, Brasília (DF), Brasil.

In Brazil, the promotion, protection, and recovery of health are among the initiatives provided by the public and universal Unified Health System (SUS). The primary healthcare level (PHC), the preferred point of access to the system, plays the role of coordinating and ordinating health care services and actions in the network. In the context of PHC, feeding and nutrition efforts must be aligned with National Feeding and Nutrition Policy (PNAN) guidelines and may be supported by feeding and nutritional surveillance actions. Data from PHC information systems and population surveys show that excess weight affects more than half the adult population of Brazil, and that consumption of ultra-processed foods is on the rise. This scenario requires that health care teams be prepared to prioritize initiatives for users with chronic diseases, using risk stratification, stabilization of the disease, and enhancement of supported self-care with a focus on diet and physical activity. At the same time, considering the country's epidemiological profile, teams must carry out initiatives to fight undernutrition and prevent anemia and hypovitaminosis A to address the multiple burden of malnutrition. The present article describes the current scenario of feeding and nutrition initiatives implemented at the PHC level in Brazil via the SUS.
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http://dx.doi.org/10.26633/RPSP.2020.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189826PMC
April 2020

Common mental disorders prevalence in adolescents: A systematic review and meta-analyses.

PLoS One 2020 23;15(4):e0232007. Epub 2020 Apr 23.

Graduate Program in Human Nutrition, University of Brasilia, Federal District, Brasilia, Brazil.

An increasing number of original studies suggest the relevance of assessing mental health; however, there has been a lack of knowledge about the magnitude of Common Mental Disorders (CMD) in adolescents worldwide. This study aimed to estimate the prevalence of CMD in adolescents, from the General Health Questionnaire (GHQ-12). Only studies composed by adolescents (10 to 19 years old) that evaluated the CMD prevalence according to the GHQ-12 were considered. The studies were searched in Medline, Embase, Scopus, Web of Science, Lilacs, Adolec, Google Scholar, PsycINFO and Proquest. In addition, the reference lists of relevant reports were screened to identify potentially eligible articles. Studies were selected by independent reviewers, who also extracted data and assessed risk of bias. Meta-analyses were performed to summarize the prevalence of CMD and estimate heterogeneity across studies. A total of 43 studies were included. Among studies that adopted the cut-off point of 3, the prevalence of CMD was 31.0% (CI 95% 28.0-34.0; I2 = 97.5%) and was more prevalent among girls. In studies that used the cut-off point of 4, the prevalence of CMD was 25.0% (CI 95% 19.0-32.0; I2 = 99.8%). Global prevalence of CMD in adolescents was 25.0% and 31.0%, using the GHQ cut-off point of 4 and 3, respectively. These results point to the need to include mental health as an important component of health in adolescence and to the need to include CMD screening as a first step in the prevention and control of mental disorders.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232007PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179924PMC
July 2020

Study of viability of high pressure extract from pomegranate peel to improve carrot juice characteristics.

Food Funct 2020 Apr;11(4):3410-3419

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

Extracts from fruit processing by-products usually present high amounts of bioactive compounds with several important activities such as antioxidant and antimicrobial capacities. In this work we studied (i) the cytotoxicity profile of pomegranate peel extract and (ii) safety and quality aspects after incorporating this extract in carrot juice - a beverage with low antioxidant potential and highly prone to microbial growth. The extract was obtained by high-pressure extraction and was non-cytotoxic towards the Caco-2 cell line after in vitro digestion. The non-cytotoxic pomegranate peel extract was added to carrot juice in a concentration of 5 mg mL-1. Fortified juices were processed by high-pressure and conventional heat and stored under refrigeration. On the 28th day of storage, microbial counts in PPE-fortified juices were reduced by 1.0 log10 CFU mL-1 and the pressurized juices showed significantly fewer counts than the thermal-treated ones. Just after processing, phenolic and flavonoid contents, as well as ABTS and FRAP antioxidant capacities, increased 3.6, 3.5, 8.2, and 9.4-fold, respectively in the fortified juices. The extract addition did not affect any colour parameter and all studied physicochemical parameters i.e. total soluble solids, pH, colour, total phenolics, flavonoids, hydrolysable tannins, and antioxidant capacity remained constant throughout storage. These findings could pave the way towards the development of safe beverages with improved bioactive properties.
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http://dx.doi.org/10.1039/c9fo02922bDOI Listing
April 2020

Correction to: Assessing genotype-phenotype associations in three dorsal colour morphs in the meadow spittlebug Philaenus spumarius (L.) (Hemiptera: Aphrophoridae) using genomic and transcriptomic resources.

BMC Genet 2020 Mar 24;21(1):36. Epub 2020 Mar 24.

Computational Biology and Population Genomics Group, cE3c - Centre for Ecology, Evolution and Environmental Changes, Departamento de Biologia Animal, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, P-1749-016, Lisbon, Portugal.

Following publication of the original article [1], it has been brought to the authors' attention that in their paper (Rodrigues et al. 2016) they reported the genome size based on 2C values (diploid genome) when it is more common to present it as 1C value.
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http://dx.doi.org/10.1186/s12863-020-00842-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092421PMC
March 2020

Valorization of Fish by-products: Purification of Bioactive Peptides from Codfish Blood and Sardine Cooking Wastewaters by Membrane Processing.

Membranes (Basel) 2020 Mar 13;10(3). Epub 2020 Mar 13.

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

Codfish blood and sardine cooking wastewaters were processed using membrane ultrafiltration that allowed for the preparation of bioactive peptides enriched fractions. The raw materials and corresponding permeates were characterized chemically and in terms of biological properties. The fractionation process was evaluated by analyzing the selective permeation of small peptides (<1 kDa) from larger compounds when using membranes with different molecular weight cut-offs (MWCOs) combined with different materials (MW, PW, and UP010 for codfish blood) and when operated at different transmembrane pressures (with GH for sardine cooking wastewaters). A rejection of the protein/peptides >10 kDa was achieved for both raw materials with the studied membranes. Also, low values of rejection of peptides <1 kDa were accomplished, namely 2% with UP010 from codfish blood and 23% when operated at minimum pressure (1.0 bar) with GH from sardine wastewaters. The peptide fractions from codfish blood with MW and UP010 exhibited the highest ABTS and ORAC values. Peptide fractions from sardine wastewaters with GH demonstrated no improvement in antioxidant activity compared to sardine wastewaters. The antimicrobial results showed that the peptide fractions from codfish blood with UP010 and from sardine with GH at 1.0 bar were capable of inhibiting growth.
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http://dx.doi.org/10.3390/membranes10030044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143626PMC
March 2020

Beneficial Propionibacteria within a Probiotic Emmental Cheese: Impact on Dextran Sodium Sulphate-Induced Colitis in Mice.

Microorganisms 2020 Mar 7;8(3). Epub 2020 Mar 7.

STLO, INRA, Agrocampus Ouest, 35 000 Rennes, France.

Backgrounds And Aims: Inflammatory Bowel Diseases (IBD), including Ulcerative Colitis (UC), coincide with alterations in the gut microbiota. Consumption of immunomodulatory strains of probiotic bacteria may induce or prolong remission in UC patients. Fermented foods, including cheeses, constitute major vectors for bacteria consumption. New evidences revealed anti-inflammatory effects in selected strains of . We thus hypothesized that consumption of a functional cheese, fermented by such a strain, may exert a positive effect on IBD.

Methods: We investigated the impact of cheese fermented by on gut inflammation. We developed an experimental single-strain cheese solely fermented by a selected immunomodulatory strain of , CIRM-BIA 129. We moreover produced, in industrial conditions, an Emmental cheese using the same strain, in combination with CNRZ327 and LMD-9, as starters. Consumption of both cheeses was investigated with respect to prevention of Dextran Sodium Sulphate (DSS)-induced colitis in mice.

Results: Consumption of the single-strain experimental cheese, or of the industrial Emmental, both fermented by CIRM-BIA 129, reduced severity of subsequent DSS-induced colitis, weight loss, disease activity index and histological score. Both treatments, in a preventive way, reduced small bowel Immunoglobulin A (IgA) secretion, restored occludin gene expression and prevented induction of Tumor Necrosis Factor α (TNFα), Interferon γ (IFNγ) and Interleukin-17 (IL-17).

Conclusions: A combination of immunomodulatory strains of starter bacteria can be used to manufacture an anti-inflammatory cheese, as revealed in an animal model of colitis. This opens new perspectives for personalised nutrition in the context of IBD.
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http://dx.doi.org/10.3390/microorganisms8030380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142753PMC
March 2020

A new MAP-Rasagiline conjugate reduces α-synuclein inclusion formation in a cell model.

Pharmacol Rep 2020 Apr 15;72(2):456-464. Epub 2020 Jan 15.

Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Göttingen, Göttingen, Germany.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease of the elderly. Current therapies are only symptomatic, and have no disease-modifying effect. Therefore, disease progresses continuously over time, presenting with both motor and non-motor features. The precise molecular basis for PD is still elusive, but the aggregation of the protein alpha-synuclein (α-syn) is a key pathological hallmark of the disease and is, therefore, a major focus of current research. Considering the intrinsic properties of cell-penetrating peptides (CPPs) for mediating drug delivery of neurotherapeutics across the blood brain barrier (BBB), these might open novel opportunities for the development of new solutions for the treatment of brain-related aspects of PD and other neurodegenerative disorders.

Methods: Here, we synthesized solid-phase CPPs using an amphipathic model peptide (MAP) conjugated with the drug Rasagiline (RAS), which we named RAS-MAP, and evaluated its effect on α-syn inclusion formation in a human cell-based model of synucleinopathy.

Results: We found that treatment with RAS-MAP at low concentrations (1-3 µM) reduced α-syn aggregation in cells.

Conclusions: For the first time, we report that conjugation of a current drug used in the therapy of PD with CPP reduces α-syn aggregation, which might prove beneficial in PD and other synucleinopathies.
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http://dx.doi.org/10.1007/s43440-019-00032-xDOI Listing
April 2020

Using Rapid Chlorophyll Fluorescence Transients to Classify Genotypes.

Plants (Basel) 2020 Feb 1;9(2). Epub 2020 Feb 1.

Biosystems and Integrative Sciences Institute (BioISI), Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal.

When a dark-adapted leaf is illuminated with saturating light, a fast polyphasic rise of fluorescence emission (Kautsky effect) is observed. The shape of the curve is dependent on the molecular organization of the photochemical apparatus, which in turn is a function of the interaction between genotype and environment. In this paper, we evaluate the potential of rapid fluorescence transients, aided by machine learning techniques, to classify plant genotypes. We present results of the application of several machine learning algorithms (k-nearest neighbors, decision trees, artificial neural networks, genetic programming) to rapid induction curves recorded in different species and cultivars of vine grown in the same environmental conditions. The phylogenetic relations between the selected species and cultivars were established with molecular markers. Both neural networks (71.8%) and genetic programming (75.3%) presented much higher global classification success rates than k-nearest neighbors (58.5%) or decision trees (51.6%), genetic programming performing slightly better than neural networks. However, compared with a random classifier (success rate = 14%), even the less successful algorithms were good at the task of classifying. The use of rapid fluorescence transients, handled by genetic programming, for rapid preliminary classification of genotypes is foreseen as feasible.
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http://dx.doi.org/10.3390/plants9020174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076723PMC
February 2020

Effect of high hydrostatic pressure extraction on biological activities of stinging nettle extracts.

Food Funct 2020 Jan;11(1):921-931

QOPNA & LAQV-REQUIMTE, Departamento de Química, Campus Universitário de Santiago Universidade de Aveiro, 3810-193 Aveiro, Portugal.

Stinging nettle is traditionally used as a therapeutic herb. In the present work, the biological properties and toxicity of novel nettle leaf extracts obtained by high pressure assisted extraction (HPE) were studied and compared with similar extracts obtained with the same solvent under atmospheric pressure conditions. The studied extracts were obtained at pressure levels of 200 and 500 MPa, ≈10 min, 0 to 70% ethanol : water (v/v). Each extract was characterized for its individual compound profile and different biological properties, such as antioxidant activity, pro-oxidant activity (DNA degradation capacity) and antihypertensive activity, as well as cytotoxicity against Caco-2 and HaCat cell cultures. The main results indicate that in addition to the antioxidant and antihypertensive activities observed for the control extracts, a clear improvement of all the biological activities of the extracts obtained by HPE was observed. The extracts obtained at 200 MPa, 10 min, 35 and 70% ethanol were the ones presenting higher concentrations of phenolic acids and flavonoids, such as chlorogenic acid, isoferulic acid, and rutin; besides, they showed better results concerning all the studied biological activities. Those extracts also showed potential for DNA protection, since they were able not only to cause less damage in the DNA molecule than the controls, but also showed no pro-oxidant activity. Concerning cytotoxicity, it was observed that HPE extracts, at a concentration up to 1.0 mg mL-1, presented a metabolism inhibition below 10 and 15% for Caco-2 and HaCat cell lines, respectively.
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http://dx.doi.org/10.1039/c9fo02442eDOI Listing
January 2020

Probiotic requires SlpB protein to mitigate mucositis induced by chemotherapy.

Oncotarget 2019 Dec 31;10(68):7198-7219. Epub 2019 Dec 31.

Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brasil.

CIRM-BIA 129 ( wild type, WT) is a probiotic bacterium, which exerts immunomodulatory effects. This strain possesses extractable surface proteins, including SlpB, which are involved in anti-inflammatory effect and in adhesion to epithelial cells. We decided to investigate the impact of gene mutation on immunomodulation and . In an assay, WT reduced expression of IL-8 (p<0.0001) and TNF-α (p<0.0001) cytokines in LPS-stimulated HT-29 cells. Δ, lacking the SlpB protein, failed to do so. Subsequently, both strains were investigated in a 5-FU-induced mucositis mice model. Mucositis is a common side effect of cytotoxic chemotherapy with 5-FU, characterized by mucosal injury, inflammation, diarrhea, and weight loss. The WT strain prevented weight loss, reduced inflammation and consequently histopathological scores. Furthermore, it regulated key markers, including Claudin-1 , p<0.0005) and IL-17a (, p<0.0001) genes, as well as IL-12 (p<0.0001) and IL-1β (p<0.0429) cytokines levels. Mutant strain displayed opposite regulatory effect on expression and on IL-12 levels. This work emphasizes the importance of SlpB in ability to reduce mucositis inflammation. It opens perspectives for the development of probiotic products to decrease side effects of chemotherapy using GRAS bacteria with immunomodulatory surface protein properties.
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http://dx.doi.org/10.18632/oncotarget.27319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944450PMC
December 2019

Evolving knowledge graph similarity for supervised learning in complex biomedical domains.

BMC Bioinformatics 2020 Jan 3;21(1). Epub 2020 Jan 3.

LASIGE, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal.

Background: In recent years, biomedical ontologies have become important for describing existing biological knowledge in the form of knowledge graphs. Data mining approaches that work with knowledge graphs have been proposed, but they are based on vector representations that do not capture the full underlying semantics. An alternative is to use machine learning approaches that explore semantic similarity. However, since ontologies can model multiple perspectives, semantic similarity computations for a given learning task need to be fine-tuned to account for this. Obtaining the best combination of semantic similarity aspects for each learning task is not trivial and typically depends on expert knowledge.

Results: We have developed a novel approach, evoKGsim, that applies Genetic Programming over a set of semantic similarity features, each based on a semantic aspect of the data, to obtain the best combination for a given supervised learning task. The approach was evaluated on several benchmark datasets for protein-protein interaction prediction using the Gene Ontology as the knowledge graph to support semantic similarity, and it outperformed competing strategies, including manually selected combinations of semantic aspects emulating expert knowledge. evoKGsim was also able to learn species-agnostic models with different combinations of species for training and testing, effectively addressing the limitations of predicting protein-protein interactions for species with fewer known interactions.

Conclusions: evoKGsim can overcome one of the limitations in knowledge graph-based semantic similarity applications: the need to expertly select which aspects should be taken into account for a given application. Applying this methodology to protein-protein interaction prediction proved successful, paving the way to broader applications.
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http://dx.doi.org/10.1186/s12859-019-3296-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942314PMC
January 2020

Monozygotic Twins Concordant for Common Variable Immunodeficiency: Strikingly Similar Clinical and Immune Profile Associated With a Polygenic Burden.

Front Immunol 2019 22;10:2503. Epub 2019 Nov 22.

Faculdade de Medicina, Instituto de Medicina Molecular João Lobo Antunes, Universidade de Lisboa, Lisbon, Portugal.

Monozygotic twins provide a unique opportunity to better understand complex genetic diseases and the relative contribution of heritable factors in shaping the immune system throughout life. Common Variable Immunodeficiency Disorders (CVID) are primary antibody defects displaying wide phenotypic and genetic heterogeneity, with monogenic transmission accounting for only a minority of the cases. Here, we report a pair of monozygotic twins concordant for CVID without a family history of primary immunodeficiency. They featured a remarkably similar profile of clinical manifestations and immunological alterations at diagnosis (established at age 37) and along the subsequent 15 years of follow-up. Interestingly, whole-exome sequencing failed to identify a monogenic cause for CVID, but unraveled a combination of heterozygous variants, with a predicted deleterious impact. These variants were found in genes involved in relevant immunological pathways, such as , and . The potential for combinatorial effects translating into the observed disease phenotype is inferred from their roles in immune pathways, namely in T and B cell activation. The combination of these genetic variants is also likely to impose a significant constraint on environmental influences, resulting in a similar immunological phenotype in both twins, despite exposure to different living conditions. Overall, these cases stress the importance of integrating NGS data with clinical and immunological phenotypes at the single-cell level, as provided by multi-dimensional flow-cytometry, in order to understand the complex genetic landscape underlying the vast majority of patients with CVID, as well as those with other immunodeficiencies.
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http://dx.doi.org/10.3389/fimmu.2019.02503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882918PMC
November 2020

The Health-Promoting Potential of spp. Bark Polar Extracts: Key Insights on Phenolic Composition and In Vitro Bioactivity and Biocompatibility.

Antioxidants (Basel) 2019 Nov 30;8(12). Epub 2019 Nov 30.

CICECO-Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.

spp. have been exploited for energy generation, along with folk medicine use of bark extracts for antipyretic and analgesic benefits. Bark phenolic components, rather than salicin, have demonstrated interesting bioactivities, which may ensure the sustainable bioprospection of bark. Therefore, this study highlights the detailed phenolic characterization, as well as the in vitro antioxidant, anti-hypertensive, growth inhibitory effects, and biocompatibility of Brot., L., and L. bark polar extracts. Fifteen phenolic compounds were characterized by ultra-high-performance liquid chromatography-ultraviolet detection-mass spectrometry analysis, from which two flavan-3-ols, an acetophenone, five flavanones, and a flavonol were detected, for the first time, as their bark components. bark extracts demonstrated strong free radical scavenging activity (5.58-23.62 µg mL IC range), effective inhibition on angiotensin-I converting enzyme (58-84%), and bactericidal action at 1250-2500 µg mL (6-8 log CFU mL reduction range). All tested bark extracts did not show cytotoxic potential against Caco-2 cells, as well as Brot. and L. extracts at 625 and 1250 µg mL against HaCaT and L929 cells. These valuable findings can pave innovative and safer food, nutraceutical, and/or cosmetic applications of bark phenolic-containing fractions.
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http://dx.doi.org/10.3390/antiox8120609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943414PMC
November 2019