Publications by authors named "José Teixeira"

489 Publications

Optimization of the Urea Linker of Triazolopyridazine MMV665917 Results in a New Anticryptosporidial Lead with Improved Potency and Predicted hERG Safety Margin.

J Med Chem 2021 Aug 3. Epub 2021 Aug 3.

Department of Chemistry, Saint Louis University, Saint Louis, Missouri 63103, United States.

Cryptosporidiosis is caused by infection of the small intestine by parasites, resulting in severe diarrhea, dehydration, malabsorption, and potentially death. The only FDA-approved therapeutic is only partially effective in young children and ineffective for immunocompromised patients. Triazolopyridazine MMV665917 is a previously reported anti- screening hit with efficacy but suffers from modest inhibition of the hERG ion channel, which could portend cardiotoxicity. Herein, we describe our initial development of structure-activity relationships of this novel lead series with a particular focus on optimization of the piperazine-urea linker. We have discovered that piperazine-acetamide is a superior linker resulting in identification of SLU-2633, which has an EC of 0.17 μM, an improved projected margin versus hERG, prolonged pharmacokinetic exposure in small intestine, and oral efficacy with minimal systemic exposure. SLU-2633 represents a significant advancement toward the identification of a new effective and safe treatment for cryptosporidiosis.
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http://dx.doi.org/10.1021/acs.jmedchem.1c01136DOI Listing
August 2021

Resveratrol Production from Hydrothermally Pretreated Eucalyptus Wood Using Recombinant Industrial Strains.

ACS Synth Biol 2021 Jul 24. Epub 2021 Jul 24.

Centre of Biological Engineering, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.

Resveratrol is a phenolic compound with strong antioxidant activity, being promising for several applications in health, food, and cosmetics. It is generally extracted from plants or chemically synthesized, in both complex and not sustainable processes, but microbial biosynthesis of resveratrol can counter these drawbacks. In this work, resveratrol production by microbial biosynthesis from lignocellulosic materials was assessed. Three robust industrial strains known for their thermotolerance and/or resistance to inhibitory compounds were identified as suitable hosts for resveratrol production from glucose and ethanol. Through the CRISPR/Cas9 system, all industrial strains, and a laboratory one, were successfully engineered with the resveratrol biosynthetic pathway the phenylalanine intermediate. All strains were further screened at 30 °C and 39 °C to evaluate thermotolerance, which is a key feature for Simultaneous Saccharification and Fermentation processes. Ethanol Red RBP showed the best performance at 39 °C, with more than 2.6-fold of resveratrol production in comparison with the other strains. This strain was then used to assess resveratrol production from glucose and ethanol. A maximum resveratrol titer of 187.07 ± 19.88 mg/L was attained from a medium with 2% glucose and 5% ethanol (w/v). Lastly, Ethanol Red RBP produced 151.65 ± 3.84 mg/L resveratrol from 2.95% of cellulose from hydrothermally pretreated wood, at 39 °C, in a Simultaneous Saccharification and Fermentation process. To the best of our knowledge, this is the first report of lignocellulosic resveratrol production, establishing grounds for the implementation of an integrated lignocellulose-to-resveratrol process in an industrial context.
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http://dx.doi.org/10.1021/acssynbio.1c00120DOI Listing
July 2021

Calcium mediated DNA binding in non-lamellar structures formed by DOPG/glycerol monooleate.

Chem Phys Lipids 2021 Jul 16;239:105118. Epub 2021 Jul 16.

Department of Physical Chemistry of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32, Bratislava, Slovakia. Electronic address:

In order to test an encapsulation method of short fragmented DNA (∼ 20-300 bp), we study the solubilisation in 150 mM solution of NaCl of a cubic phase formed by glycerol monooleate (GMO) with negatively charged dioleoylphosphatidylglycerol (DOPG) up to the level of unilamellar vesicles and, subsequently, the restoration of the cubic phase using Ca cations. We performed small angle X-ray and neutron scattering (SAXS and SANS) to follow structural changes in DOPG/GMO mixtures induced by increasing DOPG content. The cubic phase (Pn3m space group) is preserved up to ∼ 11 mol% of DOPG in DOPG/GMO. Above 20 mol%, the SANS curves are typical of unilamellar vesicles. The thickness of the DOPG/GMO lipid bilayer (d) decreases slightly with increasing fraction of DOPG. The addition of 15 mM of CaCl solution shields the electrostatic repulsions of DOPG molecules, increases slightly d and restores the cubic structures in the mixtures up to ∼ 37 mol% of DOPG. Zeta potential shows negative surface charge. The analysis of the data provides the radius of the water nano-channels of the formed non-lamellar structures. We discuss their dimensions with respect to DNA binding. In addition, Ca mediates DNA - DOPG/GMO binding. The formed hexagonal phase, H, binds less of DNA in comparison with cubic phases (∼ 6 wt% and ∼ 20 wt% of the total amount, respectively). The studied system can be utilized as anionic Q delivery vector for genetic material.
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http://dx.doi.org/10.1016/j.chemphyslip.2021.105118DOI Listing
July 2021

Purification and characterization of two new antimicrobial molecules produced by an endophytic strain of Paenibacillus polymyxa.

An Acad Bras Cienc 2021 30;93(3):e20200486. Epub 2021 Jun 30.

Programa de Pós-Graduação em Biotecnologia, Universidade Federal de São Carlos/UFSCar, Departamento de Morfologia e Patologia, Laboratório de Microbiologia e Biomoléculas, Rod. Washington Luis, Km 235, 13565-905 São Carlos, SP, Brazil.

An endophytic bacterium inhibiting pathogenic bacteria was isolated and the strain was genetically identified as Paenibacillus polymyxa. Biochemical characterization of fermentation broth indicated the presence of peptidic antimicrobial molecules. Liquid-liquid partition resulted in an organic fraction (OF) and an aqueous fraction (AF). OF presented a broad spectrum of activity against a panel of pathogenic bacteria and a fungus whereas the AF was active only against Gram-negative bacteria. AF was sequentially submitted to ion-exchange, desalting and reverse phase (RP) chromatography. A molecule with an RT of 2.45 min exhibited activity against all Gram-negative pathogenic strains tested beside P. mirabilis. The primary structure of the molecule, named AMP-Pp, was determined as Gly-Glu-Hyp-Gly-Ala by N-terminal sequencing. The molecular mass and amino acid sequence were confirmed by MS/MS. With a molecular mass of 463 Da, AMP-Pp is one of the smallest active natural peptides reported, yet. RP chromatography of OF resulted in four peaks. The first three peaks corresponded to known antimicrobials. MS analysis of peak 4 revealed the presence of an ion with m/z 3,376.4 Da, whose proposed molecular formula is C182H321N29O29. The compound, named polycerradin, showed a spectrum of activity against Gram-positive bacteria, Gram-negative bacteria (beside P. mirabilis) and a fungus.
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http://dx.doi.org/10.1590/0001-3765202120200486DOI Listing
July 2021

Anthocyanin Recovery from Grape by-Products by Combining Ohmic Heating with Food-Grade Solvents: Phenolic Composition, Antioxidant, and Antimicrobial Properties.

Molecules 2021 Jun 24;26(13). Epub 2021 Jun 24.

CBQF-Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa, Rua Arquiteto Lobão Vital 172, 4200-374 Porto, Portugal.

Usually, wine-making by-products are discarded, presenting a significant environmental impact. However, they can be used as a source of bioactive compounds. Moreover, consumers' increasing demand for naturally nutritious and healthy products requires new formulations and food product improvement, together with sustainable, environmentally friendly extraction methods. Thus, this work aimed to compare ohmic heating (OH) with conventional methodology (CONV), using food-grade solvents, mainly water, compared to standard methanol extraction of anthocyanins. No significant differences were found between the CONV and OH for total phenolic compounds, which were 2.84 ± 0.037 and 3.28 ± 0.46 mg/g DW gallic acid equivalent, respectively. The same tendency was found for antioxidant capacity, where CONV and OH presented values of 2.02 ± 0.007 g/100 g and 2.34 ± 0.066 g/100 g ascorbic acid equivalent, respectively. The major anthocyanins identified were malvidin-3--acetylglucoside, delphinidin-3--glucoside, petunidine-3--glucoside, cyanidin-3--glucoside, and peonidine-3--glucoside. These extracts displayed antimicrobial potential against microorganisms such as , , , methicillin-sensitive , a methicillin-resistant (MRSA), and . In conclusion, OH provides similar recovery yields with reduced treatment times, less energy consumption, and no need for organic solvents (green extraction routes). Thus, OH combined with water and citric acid allows a safe anthocyanin extraction from grape by-products, thus avoiding the use of toxic solvents such as methanol, and with high biological potential, including antimicrobial and antioxidant activity.
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http://dx.doi.org/10.3390/molecules26133838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270259PMC
June 2021

The Alterations of Mitochondrial Function during NAFLD Progression-An Independent Effect of Mitochondrial ROS Production.

Int J Mol Sci 2021 Jun 25;22(13). Epub 2021 Jun 25.

Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, Poland.

The progression of non-alcoholic fatty liver (NAFL) into non-alcoholic steatohepatitis implicates multiple mechanisms, chief of which is mitochondrial dysfunction. However, the sequence of events underlying mitochondrial failure are still poorly clarified. In this work, male C57BL/6J mice were fed with a high-fat plus high-sucrose diet for 16, 20, 22, and 24 weeks to induce NAFL. Up to the 20th week, an early mitochondrial remodeling with increased OXPHOS subunits levels and higher mitochondrial respiration occurred. Interestingly, a progressive loss of mitochondrial respiration along "Western diet" feeding was identified, accompanied by higher susceptibility to mitochondrial permeability transition pore opening. Importantly, our findings prove that mitochondrial alterations and subsequent impairment are independent of an excessive mitochondrial reactive oxygen species (ROS) generation, which was found to be progressively diminished along with disease progression. Instead, increased peroxisomal abundance and peroxisomal fatty acid oxidation-related pathway suggest that peroxisomes may contribute to hepatic ROS generation and oxidative damage, which may accelerate hepatic injury and disease progression. We show here for the first time the sequential events of mitochondrial alterations involved in non-alcoholic fatty liver disease (NAFLD) progression and demonstrate that mitochondrial ROS are not one of the first hits that cause NAFLD progression.
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http://dx.doi.org/10.3390/ijms22136848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268944PMC
June 2021

A mitochondria-targeted caffeic acid derivative reverts cellular and mitochondrial defects in human skin fibroblasts from male sporadic Parkinson's disease patients.

Redox Biol 2021 09 8;45:102037. Epub 2021 Jun 8.

PhD Programme in Experimental Biology and Biomedicine (PDBEB), Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal. Electronic address:

Parkinson's Disease (PD) is a neurodegenerative disorder affecting more than 10 million people worldwide. Currently, PD has no cure and no early diagnostics methods exist. Mitochondrial dysfunction is presented in the early stages of PD, and it is considered an important pathophysiology component. We have previously developed mitochondria-targeted hydroxycinnamic acid derivatives, presenting antioxidant and iron-chelating properties, and preventing oxidative stress in several biological models of disease. We have also demonstrated that skin fibroblasts from male sporadic PD patients (sPD) presented cellular and mitochondrial alterations, including increased oxidative stress, hyperpolarized and elongated mitochondria and decreased respiration and ATP levels. We also showed that forcing mitochondrial oxidative phosphorylation (OXPHOS) in sPD fibroblasts uncovers metabolic defects that were otherwise hidden. In this work, we tested the hypothesis that a lead mitochondria-targeted hydroxycinnamic acid derivative would revert the phenotype found in skin fibroblasts from sPD patients. Our results demonstrated that treating human skin fibroblasts from sPD patients with non-toxic concentrations of AntiOxCIN restored mitochondrial membrane potential and mitochondrial fission, decreased autophagic flux, and enhanced cellular responses to stress by improving the cellular redox state and decreasing reactive oxygen species (ROS) levels. Besides, fibroblasts from sPD patients treated with AntiOxCIN showed increased maximal respiration and metabolic activity, converting sPD fibroblasts physiologically more similar to their sex- and age-matched healthy controls. The positive compound effect was reinforced using a supervised machine learning model, confirming that AntiOxCIN treatment converted treated fibroblasts from sPD patients closer to the phenotype of control fibroblasts. Our data points out a possible mechanism of AntiOxCIN action contributing to a deeper understanding of how the use of mitochondria-targeted antioxidants based on a polyphenol scaffold can be used as potential drug candidates for delaying PD progression, validating the use of fibroblasts from sPD patients with more active OXPHOS as platforms for mitochondria-based drug development.
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http://dx.doi.org/10.1016/j.redox.2021.102037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220403PMC
September 2021

Novel concept of exosome-like liposomes for the treatment of Alzheimer's disease.

J Control Release 2021 Jun 11;336:130-143. Epub 2021 Jun 11.

Centre of Molecular and Environmental Biology (CBMA), Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal; IB-S - Institute of Science and Innovation for Sustainability, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal. Electronic address:

Exosomes are cell-derived vesicles that act as carriers for proteins and nucleic acids, with therapeutic potential and high biocompatibility. We propose a new concept of exosome-like liposomes for controlled delivery. The goal of this work was to develop a new type of liposomes with a unique mixture of phospholipids, similar to naturally occurring exosomes but overcoming their limitations of heterogeneity and low productivity, for therapeutic delivery of bioactive compounds. Curcumin was chosen as model compound, as it is a phytochemical molecule known to have antioxidant and anti-inflammatory properties, which can protect the brain against oxidative stress and reduce β-amyloid accumulation, major hallmarks of Alzheimer's disease (AD). These new liposomes can efficiently encapsulate hydrophobic curcumin, yielding particles with a size smaller than 200 nm, and a polydispersity index lower than 0.20, which make them ideal for crossing the blood-brain barrier. These particles have a long shelf life, being stable up to 6 months. The curcumin encapsulation efficiency was higher than 85% (up to approximately 94%). Curcumin-loaded liposomes were not cytotoxic (up to 20 μM curcumin, and 200 μM of exo-liposomes), and significantly reduced oxidative stress induced in SH-SY5Y neuronal cells, indicating their potential for neuroprotection. They also do not show any toxicity and are internalized in zebrafish embryos, concentrating in lipid enriched areas, as the brain and the yolk sac. Such innovative carriers are a new effective approach to deliver drugs into the brain, as these are stable, protect the cargo and are uptaken by neuronal cells. Upon internalization, liposomes release the therapeutic biomolecules, resulting in successful neuroprotection, being a positive alternative strategy for AD therapy.
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http://dx.doi.org/10.1016/j.jconrel.2021.06.018DOI Listing
June 2021

Summary of the Proceedings of the Basic Science of Uterine Fibroids Meeting: New Developments February 28, 2020.

F S Sci 2021 Feb 7;2(1):88-100. Epub 2020 Nov 7.

Department of Environmental and Occupational Health, George Washington University, Milken School of Public Health.

Scientists from multiple basic disciplines and an international group of physician-scientists from the field of obstetrics and gynecology presented recent studies and discussed new and evolving theories of uterine fibroid etiology, growth and development at The Basic Science of the Uterine Fibroids meeting, sponsored by the Campion Fund and the National Institute of Environmental Health Sciences. The purpose was to share up-to date knowledge and to stimulate new concepts regarding the basic molecular biology and pathophysiology of uterine fibroids, and to promote future collaborations. The meeting was held at the National Institutes of Environmental Health Sciences in North Carolina on February 28, 2020. Speakers reviewed recent advances in cellular and molecular processes that contribute to fibroid growth and new opportunities for treatment. At the conclusion of the conference, attendees identified important new directions for future research.
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http://dx.doi.org/10.1016/j.xfss.2020.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192074PMC
February 2021

Bridging the Gap Between Nature and Antioxidant Setbacks: Delivering Gallic Acid to Mitochondria.

Methods Mol Biol 2021 ;2275:161-172

CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal.

Research on mitochondria-targeted active molecules became a hot topic in the past decade. Development of mitochondria permeability transition pore (mPTP )-targeting agents with clinical applications is needed not only because of the importance of the target in several diseases but also due to the fact that the current developed molecules have shown poor clinical success. In fact, only a reduced percentage reach mitochondria , effectively preventing pathological mPTP opening. The mitochondrial-targeting strategies should be a promising solution to increase the selectivity of compounds to the mPTP , reducing also their potential side effects. Chemical conjugation of bioactive molecules with a lipophilic cation such as the triphenylphosphonium (TPP ) has been established as a robust strategy to specifically target mitochondria . Phytochemicals such as hydroxybenzoic acids are normal constituents of the human diet. These molecules display beneficial healthy effects, ranging from antioxidant action through diverse mechanisms to modulation of mitochondrial-related apoptotic system, although their therapeutic application is limited due to pharmacokinetic drawbacks. Accordingly, the development of a new antioxidant based on the dietary benzoic acid-gallic acid -is described as well as the demonstration of its mitochondriotropic characteristics.
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http://dx.doi.org/10.1007/978-1-0716-1262-0_10DOI Listing
January 2021

Exploratory Data Analysis of Cell and Mitochondrial High-Fat, High-Sugar Toxicity on Human HepG2 Cells.

Nutrients 2021 May 19;13(5). Epub 2021 May 19.

CNC-Center for Neuroscience and Cell Biology, CIBB-Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, UC-Biotech, Biocant Park, 3060-197 Cantanhede, Portugal.

Non-alcoholic steatohepatitis (NASH), one of the deleterious stages of non-alcoholic fatty liver disease, remains a significant cause of liver-related morbidity and mortality worldwide. In the current work, we used an exploratory data analysis to investigate time-dependent cellular and mitochondrial effects of different supra-physiological fatty acids (FA) overload strategies, in the presence or absence of fructose (F), on human hepatoma-derived HepG2 cells. We measured intracellular neutral lipid content and reactive oxygen species (ROS) levels, mitochondrial respiration and morphology, and caspases activity and cell death. FA-treatments induced a time-dependent increase in neutral lipid content, which was paralleled by an increase in ROS. Fructose, by itself, did not increase intracellular lipid content nor aggravated the effects of palmitic acid (PA) or free fatty acids mixture (FFA), although it led to an up-expression of hepatic fructokinase. Instead, F decreased mitochondrial phospholipid content, as well as OXPHOS subunits levels. Increased lipid accumulation and ROS in FA-treatments preceded mitochondrial dysfunction, comprising altered mitochondrial membrane potential (ΔΨm) and morphology, and decreased oxygen consumption rates, especially with PA. Consequently, supra-physiological PA alone or combined with F prompted the activation of caspase pathways leading to a time-dependent decrease in cell viability. Exploratory data analysis methods support this conclusion by clearly identifying the effects of FA treatments. In fact, unsupervised learning algorithms created homogeneous and cohesive clusters, with a clear separation between PA and FFA treated samples to identify a minimal subset of critical mitochondrial markers in order to attain a feasible model to predict cell death in NAFLD or for high throughput screening of possible therapeutic agents, with particular focus in measuring mitochondrial function.
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http://dx.doi.org/10.3390/nu13051723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161147PMC
May 2021

Rhamnolipids inhibit aflatoxins production in Aspergillus flavus by causing structural damages in the fungal hyphae and down-regulating the expression of their biosynthetic genes.

Int J Food Microbiol 2021 Jun 21;348:109207. Epub 2021 Apr 21.

CEB - Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal.

Aflatoxins are hepatotoxic and carcinogenic fungal secondary metabolites that usually contaminate crops and represent a serious health hazard for humans and animals worldwide. In this work, the effect of rhamnolipids (RLs) produced by Pseudomonas aeruginosa #112 on the growth and aflatoxins production by Aspergillus flavus MUM 17.14 was studied in vitro. At concentrations between 45 and 1500 mg/L, RLs reduced the mycelial growth of A. flavus by 23-40% and the production of aflatoxins by 93.9-99.5%. Purified mono-RLs and di-RLs exhibited a similar inhibitory activity on fungal growth. However, the RL mixture had a stronger inhibitory effect on aflatoxins production at concentrations up to 190 mg/L, probably due to a synergistic effect resulting from the combination of both congeners. Using transmission electron microscopy, it was demonstrated that RLs damaged the cell wall and the cytoplasmic membrane of the fungus, leading to the loss of intracellular content. This disruptive phenomenon explains the growth inhibition observed. Furthermore, RLs down-regulated the expression of genes aflC, aflE, aflP and aflQ involved in the aflatoxins biosynthetic pathway (6.4, 44.3, 38.1 and 2.0-fold, respectively), which is in agreement with the almost complete inhibition of aflatoxins production. Overall, the results herein gathered demonstrate for the first time that RLs could be used against aflatoxigenic fungi to attenuate the production of aflatoxins, and unraveled some of their mechanisms of action.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2021.109207DOI Listing
June 2021

Monitoring Accumulated Training and Match Load in Football: A Systematic Review.

Int J Environ Res Public Health 2021 04 8;18(8). Epub 2021 Apr 8.

Research Centre in Sports Sciences, Health and Human Development, 5001-801 Vila Real, Portugal.

(1) Background: Training load monitoring has become a relevant research-practice gap to control training and match demands in team sports. However, there are no systematic reviews about accumulated training and match load in football. (2) Methods: Following the preferred reporting item for systematic reviews and meta-analyses (PRISMA), a systematic search of relevant English-language articles was performed from earliest record to March 2020. The search included descriptors relevant to football, training load, and periodization. (3) Results: The literature search returned 7972 articles (WoS = 1204; Pub-Med = 869, SCOPUS = 5083, and SportDiscus = 816). After screening, 36 full-text articles met the inclusion criteria and were reviewed. Eleven of the included articles analyzed weekly training load distribution; fourteen, the weekly training load and match load distribution; and eleven were about internal and external load relationships during training. The reviewed articles were based on short-telemetry systems ( = 12), global positioning tracking systems ( = 25), local position measurement systems ( = 3), and multiple-camera systems ( = 3). External load measures were quantified with distance and covered distance in different speed zones ( = 27), acceleration and deceleration ( = 13) thresholds, accelerometer metrics ( = 11), metabolic power output ( = 4), and ratios/scores ( = 6). Additionally, the internal load measures were reported with perceived exertion ( = 16); heart-rate-based measures were reported in twelve studies ( = 12). (4) Conclusions: The weekly microcycle presented a high loading variation and a limited variation across a competitive season. The magnitude of loading variation seems to be influenced by the type of week, player's starting status, playing positions, age group, training mode and contextual variables. The literature has focused mainly on professional men; future research should be on the youth and female accumulated training/match load monitoring.
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http://dx.doi.org/10.3390/ijerph18083906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068156PMC
April 2021

The Importance of Post-Infarction Exercise Programs.

Arq Bras Cardiol 2021 04;116(4):793-794

Universidade Federal Fluminense - Medicina Clínica, Niterói, RJ - Brasil.

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http://dx.doi.org/10.36660/abc.20210109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121403PMC
April 2021

Algal proteins: Production strategies and nutritional and functional properties.

Bioresour Technol 2021 Jul 15;332:125125. Epub 2021 Apr 15.

CEB-Centre of Biological Engineering, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal. Electronic address:

Animal-based proteins are the most consumed worldwide given their well-balanced nutritional composition. However, the growing demand for animal proteins will not be sustainable due to their low conversion efficiency and high environmental footprint. Specific consumers' dietary restrictions and modern trends emphasize the importance of finding alternative sustainable non-animal sources to meet future food (and, in particular, protein) global needs. Algal biomass is considered a relevant alternative, presenting advantages over terrestrial biomass such as higher growth rate, low water consumption, no competition for arable land, carbon-neutral emissions, and production of numerous bioactive compounds. This review provides an overview of recent research advances on algae as source of proteins, including production strategies from relevant protein-producing species. Particular emphasis will be given to algae protein current applications and forthcoming challenges of their use. Nutritional and functional aspects of algae biomass or its protein-enriched fractions will be overviewed.
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http://dx.doi.org/10.1016/j.biortech.2021.125125DOI Listing
July 2021

Chemical Profile and Bioactivities of Extracts from Edible Plants Readily Available in Portugal.

Foods 2021 Mar 22;10(3). Epub 2021 Mar 22.

Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal.

Plant extracts have been proposed as alternative biocides and antioxidants to be included in a variety of food products. In this work, to assess the potential of rosemary, lemon balm, basil, tarragon, sage, and spearmint to be used as food additives, the chemical profiles and bioactivities of such plant extracts were studied. Furthermore, to evaluate the influence of extraction methods and solvents on the chemical characteristics and bioactivities of the plant extracts, two extraction methods (solid-liquid and Soxhlet extraction) and two solvents (water and ethanol 70% (/)) were tested for each plant. Groupwise summary statistics were calculated by plant, extraction method, and solvent, and linear models were built to assess the main effects of those terms and their interactions on the chemical characteristics and bioactivities of the extracts. The results revealed that all factors-type of plant, extraction method and solvent-have influence on the chemical profile and antioxidant activity of the resultant extracts. Interactions between factors were also observed. Hydroethanolic Soxhlet extracts presented the least potential as biopreservatives due to their low phenolic content and reduced antioxidant capacity. Oppositely, aqueous Soxhlet extracts and hydroethanolic solid-liquid extracts showed high contents in phenolic compounds and high antioxidant activities. In particular, the hydroethanolic solid-liquid extracts of lemon balm, spearmint, and sage presented the highest phenolic and flavonoid contents, accompanied by a high antioxidant activity, and they revealed antimicrobial activity against four pathogens ( ser. Typhimurium, , and ). These results demonstrate the potential of these natural resources to be incorporated as bioactive preservatives in foods or their packaging.
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http://dx.doi.org/10.3390/foods10030673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004287PMC
March 2021

Transcriptome Analyses of Myometrium from Fibroid Patients Reveals Phenotypic Differences Compared to Non-Diseased Myometrium.

Int J Mol Sci 2021 Mar 31;22(7). Epub 2021 Mar 31.

Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University College of Human Medicine, Grand Rapids, MI 49503, USA.

Uterine fibroid tissues are often compared to their matched myometrium in an effort to understand their pathophysiology, but it is not clear whether the myometria of uterine fibroid patients represent truly non-disease control tissues. We analyzed the transcriptomes of myometrial samples from non-fibroid patients (M) and compared them with fibroid (F) and matched myometrial (MF) samples to determine whether there is a phenotypic difference between fibroid and non-fibroid myometria. Multidimensional scaling plots revealed that M samples clustered separately from both MF and F samples. A total of 1169 differentially expressed genes (DEGs) (false discovery rate < 0.05) were observed in the MF comparison with M. Overrepresented Gene Ontology terms showed a high concordance of upregulated gene sets in MF compared to M, particularly extracellular matrix and structure organization. Gene set enrichment analyses showed that the leading-edge genes from the TGFβ signaling and inflammatory response gene sets were significantly enriched in MF. Overall comparison of the three tissues by three-dimensional principal component analyses showed that M, MF, and F samples clustered separately from each other and that a total of 732 DEGs from F vs. M were not found in the F vs. MF, which are likely understudied in the pathogenesis of uterine fibroids and could be key genes for future investigation. These results suggest that the transcriptome of fibroid-associated myometrium is different from that of non-diseased myometrium and that fibroid studies should consider using both matched myometrium and non-diseased myometrium as controls.
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http://dx.doi.org/10.3390/ijms22073618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036618PMC
March 2021

Emergent Technologies for the Extraction of Antioxidants from Prickly Pear Peel and Their Antimicrobial Activity.

Foods 2021 Mar 9;10(3). Epub 2021 Mar 9.

CBQF-Centro de Biotecnologia e Química Fina, Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa, Rua Arquiteto Lobão Vital 172, 4200-374 Porto, Portugal.

Phenolic compounds are important bioactive compounds identified in prickly pear peel that have important antioxidant and antimicrobial properties. However, conventional thermal extraction methods may reduce their bioactivity, and technologies such as high pressure (HP) and ohmic heating (OH) may help preserve them. In this study, both technologies were analyzed, individually and combined (250/500 MPa; 40/70 °C; ethanol concentration 30/70%), and compared with Soxhlet with regard to total phenolics, flavonoids, and carotenoids as well as antioxidant (ABTS, DPPH, ORAC), DNA pro-oxidant, and antimicrobial (inhibition halos, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), growth curves, and viable cells) activities of prickly pear peel extracts. Total phenolics extracted by each technology increased 103% (OH) and 98% (HP) with regard to Soxhlet, but the contents of total flavonoids and carotenoids were similar. Antioxidant activity increased with HP and OH (between 35% and 63%), and OH (70 °C) did not induce DNA degradation. The phenolic compound present in higher amounts was piscidic acid, followed by eucomic acid and citrate. In general, their extraction was significantly favored by HP and OH. Antimicrobial activity against 7 types of bacteria showed effective results only against , , and . No synergetic or additive effect was observed for HP/OH.
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http://dx.doi.org/10.3390/foods10030570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999070PMC
March 2021

Advances in Extraction Methods to Recover Added-Value Compounds from Seaweeds: Sustainability and Functionality.

Foods 2021 Mar 2;10(3). Epub 2021 Mar 2.

CEB-Centre of Biological Engineering, Campus Gualtar, University of Minho, 4710-057 Braga, Portugal.

Seaweeds are a renewable natural source of valuable macro and micronutrients that have attracted the attention of the scientists in the last years. Their medicinal properties were already recognized in the ancient traditional Chinese medicine, but only recently there has been a considerable increase in the study of these organisms in attempts to demonstrate their health benefits. The extraction process and conditions to be used for the obtention of value-added compounds from seaweeds depends mainly on the desired final product. Thermochemical conversion of seaweeds, using high temperatures and solvents (including water), to obtain high-value products with more potential applications continues to be an industrial practice, frequently with adverse impact on the environment and products' functionality. However more recently, alternative methods and approaches have been suggested, searching not only to improve the process performance, but also to be less harmful for the environment. A biorefinery approach display a valuable idea of solving economic and environmental drawbacks, enabling less residues production close to the much recommended zero waste system. The aim of this work is to report about the new developed methods of seaweeds extractions and the potential application of the components extracted.
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http://dx.doi.org/10.3390/foods10030516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998159PMC
March 2021

In Vitro Gastrointestinal Digestion Impact on the Bioaccessibility and Antioxidant Capacity of Bioactive Compounds from Tomato Flours Obtained after Conventional and Ohmic Heating Extraction.

Foods 2021 Mar 7;10(3). Epub 2021 Mar 7.

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

In times of pandemic and when sustainability is in vogue, the use of byproducts, such as fiber-rich tomato byproducts, can be an asset. There are still no studies on the impact of extraction methodologies and the gastrointestinal tract action on bioactive properties. Thus, this study used a solid fraction obtained after the conventional method (SFCONV) and a solid fraction after the ohmic method (SFOH) to analyze the effect of the gastrointestinal tract on bioactive compounds (BC) and bioactivities. Results showed that the SFOH presents higher total fiber than SFCONV samples, 62.47 ± 1.24-59.06 ± 0.67 g/100 g DW, respectively. Both flours present high amounts of resistant protein, representing between 11 and 16% of insoluble dietary fiber. Furthermore, concerning the total and bound phenolic compounds, the related antioxidant activity measured by 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) radical cation decolorization assay presented significantly higher values for SFCONV than SFOH samples ( < 0.05). The main phenolic compounds identified in the two flours were gallic acid, rutin, and -coumaric acid, and carotenoids were lycopene, phytofluene, and lutein, all known as health promoters. Despite the higher initial values of SFCONV polyphenols and carotenoids, these BCs' OH flours were more bioaccessible and presented more antioxidant capacity than SFCONV flours, throughout the simulated gastrointestinal tract. These results confirm the potential of ohmic heating to modify the bioaccessibility of tomato BC, enhancing their concentrations and improving their antioxidant capacity.
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http://dx.doi.org/10.3390/foods10030554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002034PMC
March 2021

Spontaneous Selection of Drug Resistance in a Calf Model of Infection.

Antimicrob Agents Chemother 2021 05 18;65(6). Epub 2021 May 18.

Cellular, Molecular and Biomedical Sciences Graduate Program, University of Vermont, Burlington, Vermont, USA

The intestinal protozoan is a leading cause of diarrheal disease and mortality in young children. There is currently no fully effective treatment for cryptosporidiosis, which has stimulated interest in anticryptosporidial development over the last ∼10 years, with numerous lead compounds identified, including several tRNA synthetase inhibitors. Here, we report the results of a dairy calf efficacy trial of the methionyl-tRNA ( MetRS [MetRS]) synthetase inhibitor 2093 and the spontaneous emergence of drug resistance. Dairy calves experimentally infected with initially improved with 2093 treatment, but parasite shedding resumed in two of three calves on treatment day 5. Parasites shed by each recrudescent calf had different amino acid-altering mutations in the gene encoding MetRS (), yielding either an aspartate 243-to-glutamate (D243E) or a threonine 246-to-isoleucine (T246I) mutation. Transgenic parasites engineered to have either the D243E or T246I MetRS mutation using CRISPR/Cas9 grew normally but were highly 2093 resistant; the D243E and T246I mutant-expressing parasites, respectively, had 2093 half-maximal effective concentrations (ECs) that were 613- and 128-fold that of transgenic parasites with wild-type MetRS. In studies using recombinant enzymes, the D243E and T246I mutations shifted the 2093 IC >170-fold. Structural modeling of MetRS based on an inhibitor-bound MetRS crystal structure suggested that the resistance mutations reposition nearby hydrophobic residues, interfering with compound binding while minimally impacting substrate binding. This is the first report of naturally emerging drug resistance, highlighting the need to address the potential for anticryptosporidial resistance and establish strategies to limit its occurrence.
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http://dx.doi.org/10.1128/AAC.00023-21DOI Listing
May 2021

Valorisation of rejected unripe plantain fruits of Musa AAB Simmonds: from nutritional characterisation to the conceptual process design for prebiotic production.

Food Funct 2021 Apr 11;12(7):3009-3021. Epub 2021 Mar 11.

Research Group on Food and Agro-industry, Department of Engineering, Universidad de Caldas, Calle 65 No. 26-10, 170004, Manizales, Colombia.

The increasing consumption of plantain fruits with specific quality standards generates high agricultural waste. This work aimed at valorising the rejected unripe pulp of Dominico-Hartón plantain fruits (Musa AAB Simmonds). The pulp was characterised physico-chemically, thermally and functionally. The data gathered experimentally and collected from different databases were used to design a production process of isomalto-oligosaccharides (IMO) syrup. The plantain flour contains high levels of starch (87 ± 2%) and amylose (31.2 ± 0.8%). The flour showed stability at high temperatures (pasting temperature of 79.26 ± 0.02 °C), allowing its use in high temperature processes. In vitro gastrointestinal digestion of the plantain flour showed that when cooked, the glycemic index of the flour increased from 47.7 ± 2.2 to 84.2 ± 1.8, while its resistant starch content only slightly decreased from 71.7 ± 1% to 52.6 ± 2%, suggesting that this type of flour preserves high content of dietary fibre after digestion. The conceptual process design showed that 24.48 g of IMO are theoretically obtained from 53.24 g of plantain flour maltose. These results suggest that the rejected plantain pulp holds high potential as an ingredient for the production of prebiotic compounds such as IMO.
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http://dx.doi.org/10.1039/d0fo03379kDOI Listing
April 2021

Likelihood of injury due to vasovagal syncope: a systematic review and meta-analysis.

Europace 2021 Jul;23(7):1092-1099

Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, Alberta T2N 4Z6, Canada.

Aims: Vasovagal syncope (VVS) is the most common type of syncope and is usually considered a benign disorder. The potential for injury is worrisome but the likelihood is unknown. We aimed to determine the proportion of patients injured due to VVS.

Methods And Results: A systematic search of studies published until August 2020 was performed in multiple medical and nursing databases. Included studies had data on the proportion of patients with injury due to VVS prior to study enrolment. Random effects methods were used. Twenty-three studies having 3593 patients met inclusion criteria. Patients were diagnosed clinically with VVS, and 82% had >2 syncopal episodes before enrolment. Tilt test was positive in 60% and 14 studies reported comorbidities (32.6% hypertensive). The weighted mean injury rate was 33.5% [95% confidence interval (CI): 27.3-40.5%]. The likelihood of injury correlated with population age (r = 0.4, P = 0.05), but not with sex, positive tilt test, or hypertension. The injury rates were 25.7% (95% CI: 19.1-32.8%) in studies with younger patients (mean age ≤50 years, n = 1803) and 43.4% (95% CI: 34.9-52.3%) in studies with older patients (P = 0.002). Nine studies reported major injuries; with a weighted mean rate of major injuries of 13.9% (95% CI: 9.5-19.8%).

Conclusion : Injuries due to syncope are frequent, occurring in 33% of patients with VVS. The risk of major injuries is substantial. Older patients are at higher risk. Clinicians should be aware of the risk of injuries when providing care and advice to patients with VVS.
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http://dx.doi.org/10.1093/europace/euab041DOI Listing
July 2021

Active natural-based films for food packaging applications: The combined effect of chitosan and nanocellulose.

Int J Biol Macromol 2021 Apr 22;177:241-251. Epub 2021 Feb 22.

Centre for Textile Science and Technology (2C2T), University of Minho, 4800-058 Guimarães, Portugal; Department of Mechanical Engineering, University of Minho, 4800-058 Guimarães, Portugal. Electronic address:

This work aimed to evaluate the potential of chitosan/cellulose nanocrystals (CNC) films to be used as active pads for meat packages to prolong its shelf-life and preserve its properties over time. Several CNC concentrations (5, 10, 25, and 50 wt%) were tested and the films were produced by solvent casting. The developed samples were characterized by ATR-FTIR, TGA, FESEM, and XRD. The transparency, antimicrobial, barrier and mechanical properties were also assessed. Finally, the films' ability to prolong food shelf-life was studied in real conditions using chicken meat. CNC incorporation improved the thermal stability and the oxygen barrier while the water vapor permeability was maintained. An enhancement of mechanical properties was also observed by the increase in tensile strength and Young's modulus in chitosan/CNC films. These films demonstrated bactericidal effect against Gram-positive and Gram-negative bacteria and fungicidal activity against Candida albicans. Lastly, chitosan-based films decreased the growth of Pseudomonas and Enterobacteriaceae bacteria in meat during the first days of storage compared to commercial membranes, while chitosan/CNC films reduced the total volatile basic nitrogen (TVB-N), indicating their efficiency in retarding meat's spoilage under refrigeration conditions. This work highlights the great potential of natural-based films to act as green alternatives for food preservation.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.105DOI Listing
April 2021

Encapsulated Pine Bark Polyphenolic Extract during Gastrointestinal Digestion: Bioaccessibility, Bioactivity and Oxidative Stress Prevention.

Foods 2021 Feb 4;10(2). Epub 2021 Feb 4.

Agrotecnio Center, Department of Food Technology, University of Lleida, 25003 Lleida, Spain.

Polyphenolic extracts from pine bark have reported different biological actions and promising beneficial effects on human health. However, its susceptibility to environmental stresses (temperature, storage, etc.) and physiological human conditions prequires the development of efficient protection mechanisms to allow effective delivering of functionality. The aim of this work was to encapsulate pine bark extract rich phenolic compounds by spray-drying using maltodextrin, and understand the influence of encapsulation on the antioxidant and antimicrobial activity and bioaccessibility of phenolic compounds during gastrointestinal digestion. The optimized process conditions allowed good encapsulation efficiency of antioxidant phenolic compounds. The microencapsulation was effective in protecting those compounds during gastrointestinal conditions, controlling their delivery and enhancing its health benefits, decreasing the production of reactive oxygen species implicated in the process of oxidative stress associated with some pathologies. Finally, this encapsulation system was able to protect these extracts against acidic matrices, making the system suitable for the nutritional enrichment of fermented foods or fruit-based beverages, providing them antimicrobial protection, because the encapsulated extract was effective against . Overall, the designed system allowed protecting and appropriately delivering the active compounds, and may find potential application as a natural preservative and/or antioxidant in food formulations or as bioactive ingredient with controlled delivery in pharmaceuticals or nutraceuticals.
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http://dx.doi.org/10.3390/foods10020328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913864PMC
February 2021

Transcription factor 4 and its association with psychiatric disorders.

Transl Psychiatry 2021 01 5;11(1):19. Epub 2021 Jan 5.

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.

The human transcription factor 4 gene (TCF4) encodes a helix-loop-helix transcription factor widely expressed throughout the body and during neural development. Mutations in TCF4 cause a devastating autism spectrum disorder known as Pitt-Hopkins syndrome, characterized by a range of aberrant phenotypes including severe intellectual disability, absence of speech, delayed cognitive and motor development, and dysmorphic features. Moreover, polymorphisms in TCF4 have been associated with schizophrenia and other psychiatric and neurological conditions. Details about how TCF4 genetic variants are linked to these diseases and the role of TCF4 during neural development are only now beginning to emerge. Here, we provide a comprehensive review of the functions of TCF4 and its protein products at both the cellular and organismic levels, as well as a description of pathophysiological mechanisms associated with this gene.
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http://dx.doi.org/10.1038/s41398-020-01138-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791034PMC
January 2021

Impact of sarcopenia in aortoiliac occlusive disease in Mediterranean population.

Turk Gogus Kalp Damar Cerrahisi Derg 2020 Oct 21;28(4):615-622. Epub 2020 Oct 21.

Department of Phisiology and Surgery, Faculdade de Medicina da Universidade do Porto, Portugal.

Background: This study aims to validate the psoas muscle area and psoas muscle density as morphometric predictors in cardiovascular and cerebrovascular endpoints in patients with extensive aortoiliac peripheral arterial disease.

Methods: A total of 57 patients (55 males, 2 females; mean age 60±8.2 years; range, 35 to 83 years) with Trans-Atlantic Inter-Society Consensus type D lesions who underwent revascularization at two Portuguese tertiary hospitals between January 2013 and July 2019 were retrospectively analyzed. The patients with a recent (<6 months) computed tomography scan prior to the revascularization procedure were included in the study. Both centers offered to their patients open and endovascular repair of aortoiliac peripheral arterial disease. Major adverse cardiovascular and cerebrovascular events and major adverse limb events were evaluated.

Results: The median follow-up was 20 months. The mean survival rate was 93±3.4% at 30 days and 62.7±8.6% at 48 months. The discriminative thresholds found in this population were 2,175.8 mm2 for total psoas area and 51.75 Hounsfield unit for psoas muscle density. There was a statistically significant difference in the one-year survival rate (p=0.003 and p=0.291, respectively) and major adverse cardiovascular and cerebrovascular events (p=0.005 and p=0.206, respectively) for total psoas area compared to psoas muscle density.

Conclusion: Total psoas area shows a prognostic value for survival and major adverse cardiovascular and cerebrovascular events in this patient population.
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http://dx.doi.org/10.5606/tgkdc.dergisi.2020.20146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759032PMC
October 2020

Conformation of Myoglobin-Poly(Ethyl Ethylene Phosphate) Conjugates Probed by SANS: Correlation with Polymer Grafting Density and Interaction.

Macromol Biosci 2021 02 4;21(2):e2000356. Epub 2021 Jan 4.

Laboratoire Léon Brillouin (CEA/CNRS), CEA Saclay, Gif-sur-Yvette, Cedex, 91191, France.

One can take advantage of the influence of a polymer conjugated with a protein to control the thermal stability and the deployment of the protein. Here, the structural properties are reported of the protein-polymer conjugate myoglobin (Mb)-poly(ethyl ethylene phosphate) (PEEP) in the native and unfolded conformations, in order to understand the respective roles of the protein and of the polymer size in the stability of the conjugate. The effect is also investigated of the grafting density of the linear biodegradable polyphosphoesters covalently attached to the protein. It is observed that, while the conjugation process at room temperature does not modify the secondary and tertiary structure of the Mb, the unfolding process, as a function of temperature, depends on the grafting density. Small angle neutron scattering reveals that, at room temperature, conjugation does not alter the size of the native protein and that the thickness of the polymer shell around the protein increases as a function of grafting density and of polymer molecular weight. The denatured form of all conjugates is described by an unfolded chain and a correlation length due to the presence of local stiffness.
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http://dx.doi.org/10.1002/mabi.202000356DOI Listing
February 2021

Mitochondria-targeted phenolic antioxidants induce ROS-protective pathways in primary human skin fibroblasts.

Free Radic Biol Med 2021 02 29;163:314-324. Epub 2020 Dec 29.

Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500HB Nijmegen, the Netherlands. Electronic address:

Phytochemical antioxidants like gallic and caffeic acid are constituents of the normal human diet that display beneficial health effects, potentially via activating stress response pathways. Using primary human skin fibroblasts (PHSFs) as a model, we here investigated whether such pathways were induced by novel mitochondria-targeted variants of gallic acid (AntiOxBEN) and caffeic acid (AntiOxCIN). Both molecules reduced cell viability with similar kinetics and potency (72 h incubation, IC50 ~23 μM). At a relatively high but non-toxic concentration (12.5 μM), AntiOxBEN and AntiOxCIN increased ROS levels (at 24 h), followed by a decline (at 72 h). Further analysis at the 72 h timepoint demonstrated that AntiOxBEN and AntiOxCIN did not alter mitochondrial membrane potential (Δψ), but increased cellular glutathione (GSH) levels, mitochondrial NAD(P)H autofluorescence, and mitochondrial superoxide dismutase 2 (SOD2) protein levels. In contrast, cytosolic SOD1 protein levels were not affected. AntiOxBEN and AntiOxCIN both stimulated the gene expression of Nuclear factor erythroid 2-related factor 2 (NRF2; a master regulator of the cellular antioxidant response toward oxidative stress). AntiOxBEN2 and ANtiOxCIN4 differentially affected the gene expression of the antioxidants Heme oxygenase 1 (HMOX1) and NAD(P)H dehydrogenase (quinone) 1 (NQO1). Both antioxidants did not protect from cell death induced by GSH depletion and AntiOxBEN (but not AntiOxCIN) antagonized hydrogen peroxide-induced cell death. We conclude that AntiOxBEN and AntiOxCIN increase ROS levels, which stimulates NRF2 expression and, as a consequence, SOD2 and GSH levels. This highlights that AntiOxBEN and AntiOxCIN can act as prooxidants thereby activating endogenous ROS-protective pathways.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.12.023DOI Listing
February 2021

Differential proteomic analysis by SWATH-MS unravels the most dominant mechanisms underlying yeast adaptation to non-optimal temperatures under anaerobic conditions.

Sci Rep 2020 12 18;10(1):22329. Epub 2020 Dec 18.

CEB - Centre of Biological Engineering, University of Minho, 4710-057, Braga, Portugal.

Elucidation of temperature tolerance mechanisms in yeast is essential for enhancing cellular robustness of strains, providing more economically and sustainable processes. We investigated the differential responses of three distinct Saccharomyces cerevisiae strains, an industrial wine strain, ADY5, a laboratory strain, CEN.PK113-7D and an industrial bioethanol strain, Ethanol Red, grown at sub- and supra-optimal temperatures under chemostat conditions. We employed anaerobic conditions, mimicking the industrial processes. The proteomic profile of these strains in all conditions was performed by sequential window acquisition of all theoretical spectra-mass spectrometry (SWATH-MS), allowing the quantification of 997 proteins, data available via ProteomeXchange (PXD016567). Our analysis demonstrated that temperature responses differ between the strains; however, we also found some common responsive proteins, revealing that the response to temperature involves general stress and specific mechanisms. Overall, sub-optimal temperature conditions involved a higher remodeling of the proteome. The proteomic data evidenced that the cold response involves strong repression of translation-related proteins as well as induction of amino acid metabolism, together with components related to protein folding and degradation while, the high temperature response mainly recruits amino acid metabolism. Our study provides a global and thorough insight into how growth temperature affects the yeast proteome, which can be a step forward in the comprehension and improvement of yeast thermotolerance.
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http://dx.doi.org/10.1038/s41598-020-77846-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749138PMC
December 2020
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