Serum phospholipidomics reveals altered lipid profile and promising biomarkers in multiple sclerosis

Multiple sclerosis is a neurodegenerative disease causing disability in young adults. Alterations in metabolism and lipid profile have been associated with this disease. Several studies have reported changes in the metabolism of arachidonic acid and the profile of fatty acids, ceramides, phospholipids and lipid peroxidation products. Nevertheless, the understanding of the modulation of circulating lipids at the molecular level in multiple sclerosis remains unclear. In the present study, we sought to assess the existence of a distinctive lipid signature of multiple sclerosis using an untargeted lipidomics approach. It also aimed to assess the differences in lipid profile between disease status (relapse and remission). For this, we used hydrophilic interaction liquid chromatography coupled with mass spectrometry for phospholipidomic profiling of serum samples from patients with multiple sclerosis. Our results demonstrated that multiple sclerosis has a phospholipidomic signature different from that of healthy controls, especially the PE, PC, LPE, ether-linked PE and ether-linked PC species. Plasmalogen PC and PE species, which are natural endogenous antioxidants, as well as PC and PE polyunsaturated fatty acid esterified species showed significantly lower levels in patients with multiple sclerosis and patients in both remission and relapse of multiple sclerosis. Our results show for the first time that the serum phospholipidome of multiple sclerosis is significantly different from that of healthy controls and that few phospholipids, with the lowest p-value, such as PC(34:3), PC(36:6), PE(40:10) and PC(38:1) may be suitable as biomarkers for clinical applications in multiple sclerosis.publishe

Virtual laboratories in (bio)chemical engineering education

In the last decades, Information and Communications Technologies (ICT) have been promoting the creation and adoption of new learning and teaching styles. Virtual laboratories, by overcoming some limitations of conventional hands-on experiments, have been adopted as a complement or in substitution of laboratory sessions. This paper describes the design and implementation of two virtual labs for biochemical engineering education intended for students at the BSc degree. One of the virtual labs is intended to fully replace the hands-on experiment and consists on the determination of the correlation between oxygen transfer rate, aeration rate and agitation power in a reactor. The other virtual lab consists on the determination of the residence time distribution (RTD) in continuous stirred tanks series and was implemented to support the physical experiments rather than replacing them. The virtual labs provide the students a learning platform covering the fundamentals underlying the experiment, its pre-visualization and simulation. The effectiveness of the implemented system was evaluated through direct experimentation and survey (through questionnaires) with students taking the chemical technology lab course. For the RTD virtual Lab, and based on specific learning outcomes, teachers could assess significant improvement in students’ performance in the lab and also a more thorough discussion of the results in the reports. The survey results show that, in average, considering the two virtual labs and several classes, 93% of the students consider the virtual labs of great utility.Universidade do Minho (UM) - “Programa Qualidade

Virtual laboratories in (bio)chemical engineering education

"Qualidade” of the Universidade do Minho

Boosting bioethanol production from Eucalyptus wood by whey incorporation

The mixture of Eucalyptus globulus wood (EGW) and cheese whey powder (CWP) was proposed for intensification of simultaneous saccharification and fermentation (SSF) at high temperature and solid loadings using the industrial Saccharomyces cerevisiae Ethanol Red® strain. High ethanol concentration (93 g/L), corresponding to 94% ethanol yield, was obtained at 35 °C from 37% of solid mixture using cellulase and -galactosidase enzymes (24.2 FPU/g and 20.0 U/g, respectively). The use of CWP mixed with pretreated EGW increased the ethanol concentration in 1.5-fold, in comparison with SSF experiments without CWP for both Ethanol Red® and CEN.PK1137D strains. Moreover, 1.4-fold higher ethanol concentration was obtained with Ethanol Red®, in comparison with CEN.PK113-7D strain. Ethanol Red® strain was genetically engineered for -galactosidase production in order to advance towards a fully integrated process. This work shows the feasibility of attaining high ethanol concentrations in second generation bioprocesses by a multi-waste valorization approach.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/ BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by European Regional Development Fund under the scope of Norte2020 – Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

Lipidomics in autoimmune diseases with main focus on systemic lupus erythematosus

Autoimmune diseases (AID) are a heterogeneous group of disorders that have in common a chronic inflammation and dysregulation of the immune system. Systemic lupus erythematosus (SLE) is one of the most frequent systemic autoimmune diseases characterized by autoimmune phenomena in multiple organs. The tests used for evolution and prognosis assessment are either non-specific or non-sensitive, impairing an adequate therapeutics. To face this drawback, lipidomics is being used to provide more knowledge and insights regarding autoimmune disorders. Through lipidomic approaches using MS, it is possible to identify and quantify the level of lipid molecular species in the biological system and this could be useful to identify biomarkers and to better understand the pathophysiology of autoimmune diseases. There are some evidence that lipids and oxidized lipids can play a key role in AID pathogenesis. Although this field has been scarcely explored, there are some studies that reported variations on the lipid profile at a molecular level using lipidomic approaches based on MS in SLE. The results gathered herein showed changes mainly in the level of phospholipids, with decrease of some plasmenyl lipids, fatty acids, with reduction of PUFA, and sphingolipids, with changes in fatty acyl chain composition. These changes may be the result of lipids` modifications due to oxidation and increase of ROS. Some alterations can be associated with changes in membrane of lymphocytes and with the deregulation of the immune system. Thus, exploring the knowledge from modern lipidomic approaches in the study of the role of lipids and oxidized lipids, in oxidative stress and in inflammatory diseases, could contribute for the identification of new lipid biomarkers. Lipid biomarkers are promising tools to prognosis and treatment monitoring, tailored for the best therapeutic response and highest safety to ensure better patient care and to be used for personalized medicine.publishe

Grid structure impact in sparse point representation of derivatives

In the Sparse Point Representation (SPR) method the principle is to retain the function data indicated by significant interpolatory wavelet coefficients, which are defined as interpolation errors by means of an interpolating subdivision scheme. Typically, a SPR grid is coarse in smooth regions, and refined close to irregularities. Furthermore, the computation of partial derivatives of a function from the information of its SPR content is performed in two steps. The first one is a refinement procedure to extend the SPR by the inclusion of new interpolated point values in a security zone. Then, for points in the refined grid, such derivatives are approximated by uniform finite differences, using a step size proportional to each point local scale. If required neighboring stencils are not present in the grid, the corresponding missing point values are approximated from coarser scales using the interpolating subdivision scheme. Using the cubic interpolation subdivision scheme, we demonstrate that such adaptive finite differences can be formulated in terms of a collocation scheme based on the wavelet expansion associated to the SPR. For this purpose, we prove some results concerning the local behavior of such wavelet reconstruction operators, which stand for SPR grids having appropriate structures. This statement implies that the adaptive finite difference scheme and the one using the step size of the finest level produce the same result at SPR grid points. Consequently, in addition to the refinement strategy, our analysis indicates that some care must be taken concerning the grid structure, in order to keep the truncation error under a certain accuracy limit. Illustrating results are presented for 2D Maxwell's equation numerical solutions

Phacoemulsification Versus Peripheral Iridotomy in the Management of Chronic Primary Angle Closure: Long-Term Follow-Up

Primary angle closure occurs as a result of crowded anterior segment anatomy, causing appositional contact between the peripheral iris and trabecular meshwork, thereby obstructing aqueous outflow. Several studies highlight the role of the crystalline lens in its pathogenesis. The objective of this work is to compare the long-term efficacy of phacoemulsification versus laser peripheral iridotomy (LPI) in the management of chronic primary angle closure (CPAC). Prospective case-control study with 30 eyes of 30 patients randomly divided in two groups: 15 eyes in the LPI group and 15 eyes in the IOL group. Patients in the LPI group underwent LPI using argon and Nd:YAG laser. Patients in the IOL group underwent phacoemulsification with posterior chamber intraocular lens (IOL) implantation. Examinations before and after the procedure included gonioscopy, Goldmann applanation tonometry, and anterior chamber evaluation using the Pentacam rotating Scheimpflug camera. The mean follow-up time was 31.13 ± 4.97 months. There was a statistically significant reduction in the intraocular pressure (IOP) and number of anti-glaucoma medications (p < 0.01) only in the IOL group. Anterior chamber depth, angle, and volume were all higher in the IOL group (p < 0.01) at the end of the follow-up period. Phacoemulsification with posterior chamber IOL implantation results in a higher anterior chamber depth, angle, and volume, when compared to LPI. Consequently, phacoemulsification has greater efficacy in lowering IOP and preventing its long-term increase in patients with CPAC and cataract

Polyphenols characterization and toxicological evaluation of pterospartum tridentatum leaf water extracts

Pterospartum tridentatum Willk. (prickled broom) is an autochthonous and common plant in Portugal. Leaves and stems are normally used in cooking, to flavour rice, roast meat or hunting animals. Leaves are also used as a condiment in fresh salads and, despite of its traditional use, no toxicological evaluation has been performed. P. tridentatum leaves aqueous extract ESI-MS spectrum revealed the presence of several luteolin and isorhamnetin derived phenolic compounds, which can be associated to the health benefits claimed for this plant species. Still, P. tridentatum leaves extract (up to 100 µg plant extract.mg-1 protein) stimulated state 4 and FCCP-stimulated liver mitochondria respiratory rates and inhibited the state 3 respiratory rate. Respiratory control ratio was diminished, indicating a decrease in phosphorylative efficiency due to inner mitochondrial membrane induced by P. tridentatum leaves extract. Nevertheless, previous results, cytotoxicity evaluation by MTT assay (50 and 125 µg plant extract) showed no significant decrease on HepG2 cell viability. Overall, the present study suggests that the consumption of P. tridentatum leaves should be regarded as safe

Toxicological evaluation of pterospartum tridentatum flower water

Pterospartum tridentatum Willk. (prickled broom) is an autochthonous plant, common in Portuguese territory. The yellow flowers are widely used in traditional medicine, as a potential cure for all body illnesses, mainly for throat irritation treatment or for diabetes, hypertension and hypercholesterolemia therapy. Despite its wide traditional use, no toxicological assessment of this plant has been performed, as far as we know. The major goal of this work was the P. tridentatum water extracts safety assessment. Methodology: Chemical characterization of MS analysis of P. tridentatum flower extract was performed by ESI-MS spectroscopy; phenols and quercetins content were also determined. Antioxidant activity was evaluated through -carotene bleaching test and ABTS radical-scavenging activity. Oxygen consumption of isolated mitochondria was determined polarographically with a Clark oxygen electrode and mitochondrial respiratory rates evaluated accordingly to Chance and Williams (1956) and mitochondrial swelling was evaluated the apparent absorbance changes at 520 nm. Results and discussion: A high antioxidant activity of P. tridentatum flower water extract was assessed in good agreement with its ESI-MS spectrum that revealed the presence of several flavonoids, as luteolin-O-(O-acetyl)-glucuronide, luteolin-Oglucuronide or isorhamnetin-O-hexoside. Mitocondrial respiratory rates (state 4, state 3 and FCCP-stimulated respiration) and respiratory indexes (respiratory control and P/O ratios) showed no consistent decrease of respiratory and phosphorylative efficiencies for the concentrations tested (up to 500 μg.mL-1). In conclusion, for the concentration range commonly used P. tridentatum flowers usage can be regarded as harmless and trustworthy and due to its great antioxidant properties it is useful to counteract diabetes mellitus associated diseases

Major anthocyanins in elderberry effectively trap methylglyoxal and reduce cytotoxicity of methylglyoxal in HepG2 cell line

The accumulation of advanced glycation end-products (AGEs) in the body is implicated in numerous diseases, being methylglyoxal (MGO) one of the main precursors. One of the strategies to reduce AGEs accumulation might be acting in an early stage of glycation by trapping MGO. Thus, this work aimed to evaluate, for the first time, the potential of elderberries polyphenols to trap MGO, access the formation of MGO adducts, and evaluate the cytoprotection effect in HepG2 and Caco-2 cells. The results demonstrated that monoglycosylated anthocyanins (cyanidin-3-glucoside and cyanidin-3-sambubioside) are very efficient in trapping MGO, forming mono- and di-adducts. Quercetin-3-glucoside and quercetin-3-rutinoside reacted slowly, while diglycosylated anthocyanins did not react. The trapping of MGO by elderberry monoglycosylated anthocyanins significantly decreased the MGO cytotoxicity in HepG2 cells (∼70 % of cell viability), while the effect in Caco-2 cells was lower (∼50 %). Thus, elderberry phenolics present antiglycation potential by trapping MGOpublishe