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Elucidating the biochemical mechanisms associated with the progression of alcoholic liver disease (ALD) to more advanced stages such as alcoholic hepatitis (AH) remains an important clinical and scientific challenge. Several hypotheses point to the involvement of advanced glycation end-products (AGEs) in alcohol-associated liver injuries. Recently, we determined the structure of a synthetic, melibiose-derived AGE (MAGE), which was an analog of the novel AGE subgroup AGE10. The primary objective of our study was to determine whether AGE10 was associated with alcoholic hepatitis. The secondary objective was to provide a diagnostic accuracy of AGE10 in AH. To achieve this objective, we examined the plasma levels of AGE10 in 65 healthy individuals and 65 patients with AH. The AGE10 level was measured using a competitive ELISA. Our study confirmed that patients with AH had significantly higher plasma concentrations of AGE10 compared with healthy controls (184.5 ± 71.1 μg/mL and 123.5 ± 44.9 μg/mL, respectively; p < 0.001). In addition, AGE10 showed an acceptable performance as a diagnostic marker of AH, with an AUC of 0.78. In conclusion, AH was associated with elevated levels of novel advanced glycation end-product AGE10. [ABSTRACT FROM AUTHOR]

MAGE (melibiose-derived advanced glycation end-product) is the glycation product generated in the reaction of a model protein with melibiose. The in vivo analog accumulates in several tissues; however, its origin still needs explanation. In vitro MAGE is efficiently generated under dry conditions in contrast to the reaction carried in an aqueous solvent. Using liquid chromatography coupled with mass spectrometry, we analyzed the physicochemical properties and structures of myoglobin glycated with melibiose under different conditions. The targeted peptide analysis identified structurally different AGEs, including crosslinking and non-crosslinking modifications associated with lysine, arginine, and histidine residues. Glycation in a dry state was more efficient in the formation of structures containing an intact melibiose moiety (21.9%) compared to glycation under aqueous conditions (15.6%). The difference was reflected in characteristic fluorescence that results from protein structural changes and impact on a heme group of the model myoglobin protein. Finally, our results suggest that the formation of in vitro MAGE adduct is initiated by coupling melibiose to a model myoglobin protein. It is confirmed by the identification of intact melibiose moieties. The intermediate glycation product can further rearrange towards more advanced structures, including cross-links. This process can contribute to a pool of AGEs accumulating locally in vivo and affecting tissue biology. [ABSTRACT FROM AUTHOR]

Understanding the key factors that play an important role in students' performance can assist improvements in the teaching-learning process. As an alternative, artificial intelligence (AI) methods have enormous potential, facilitating a new trend in education. Despite the advances, there is an open debate on the most suitable model for machine learning applied to forecast student performance patterns. This paper addresses this gap, where a comparative analysis between AI methods was performed. As a research hypothesis, a fuzzy inference system (FIS) should provide the best accuracy in this forecast task, due to its ability to deal with uncertainties. To do so, this paper introduces a model proposal based on AI using a FIS. An online survey was carried to collect data. Filling out a self-report, respondents declare how often they use some learning strategies. In addition, we also used historical records of students' grades and retention from the last 5 years before the COVID pandemic. Firstly, two experimental groups were composed of students with failing and passing grades, compared by the Mann-Whitney test. Secondly, an association between the 'frequency of using learning strategies' and 'occurrence of failing grades' was quantified using a logistic regression model. Then, a discriminant analysis was performed to build an Index of Student Performance Expectation (SPE). Considering the learning strategies with greater discriminating power, the fuzzy AI-based model was built using the database of historical records. The learning strategies with the most significant effect on students' performance were lesson review (34.6%), bibliography reading (25.6%), class attendance (23.5%), and emotion control (16.3%). The fuzzy AI-based model proposal outperformed other AI methods, achieving 94.0% accuracy during training and a generalization capacity of 91.9% over the testing dataset. As a practical implication, the SPE index can be applied as a tool to support students' planning in relation to the use of learning strategies. In turn, the AI model based on fuzzy can assist professors in identifying students at higher risk of retention, enabling preventive interventions. [ABSTRACT FROM AUTHOR]

In smart mobility, the semantic segmentation of images is an important task for a good understanding of the environment. In recent years, many studies have been made on this subject, in the field of Autonomous Vehicles on roads. Some image datasets are available for learning semantic segmentation models, leading to very good performance. However, for other types of autonomous mobile systems like Electric Wheelchairs (EW) on sidewalks, there is no specific dataset. Our contribution presented in this article is twofold: (1) the proposal of a new dataset of short sequences of exterior images of street scenes taken from viewpoints located on sidewalks, in a 3D virtual environment (CARLA); (2) a convolutional neural network (CNN) adapted for temporal processing and including additional techniques to improve its accuracy. Our dataset includes a smaller subset, made of image pairs taken from the same places in the maps of the virtual environment, but from different viewpoints: one located on the road and the other located on the sidewalk. This additional set is aimed at showing the importance of the viewpoint in the result of semantic segmentation. [ABSTRACT FROM AUTHOR]

Molecular mechanisms underlying the beneficial effect of sitagliptin repurposed for hepatic ischemia-reperfusion injury (IRI) are poorly understood. We aimed to evaluate the impact of IRI and sitagliptin on the hepatic profile of eicosanoids (LC-MS/MS) and expression/concentration (RTqPCR/ELISA) of GLP-1/GLP-1R, SDF-1α/CXCR4 and VIP/VPAC1, VPAC2, and PAC1 in 36 rats. Animals were divided into four groups and subjected to ischemia (60 min) and reperfusion (24 h) with or without pretreatment with sitagliptin (5 mg/kg) (IR and SIR) or sham-operated with or without sitagliptin pretreatment (controls and sitagliptin). PGI2, PGE2, and 13,14-dihydro-PGE1 were significantly upregulated in IR but not SIR, while sitagliptin upregulated PGD2 and 15-deoxy-12,14-PGJ2. IR and sitagliptin non-significantly upregulated GLP-1 while Glp1r expression was borderline detectable. VIP concentration and Vpac2 expression were downregulated in IR but not SIR, while Vpac1 was significantly downregulated solely in SIR. IRI upregulated both CXCR4 expression and concentration, and sitagliptin pretreatment abrogated receptor overexpression and downregulated Sdf1. In conclusion, hepatic IRI is accompanied by an elevation in proinflammatory prostanoids and overexpression of CXCR4, combined with downregulation of VIP/VPAC2. Beneficial effects of sitagliptin during hepatic IRI might be mediated by drug-induced normalization of proinflammatory prostanoids and upregulation of PGD2 and by concomitant downregulation of SDF-1α/CXCR4 and reinstating VIP/VCAP2 signaling. [ABSTRACT FROM AUTHOR]

Aging is associated with a general decline in cognitive functions, which appears to be due to alterations in the amounts of proteins involved in the regulation of synaptic plasticity. Here, we present a quantitative analysis of proteins involved in neurotransmission in three brain regions, namely, the hippocampus, the cerebral cortex and the cerebellum, in mice aged 1 and 22 months, using the total protein approach technique. We demonstrate that although the titer of some proteins involved in neurotransmission and synaptic plasticity is affected by aging in a similar manner in all the studied brain formations, in fact, each of the formations represents its own mode of aging. Generally, the hippocampal and cortical proteomes are much more unstable during the lifetime than the cerebellar proteome. The data presented here provide a general picture of the effect of physiological aging on synaptic plasticity and might suggest potential drug targets for anti-aging therapies. [ABSTRACT FROM AUTHOR]

A possibility of repurposing sitagliptin, a well-established antidiabetic drug, for alleviating injury caused by ischemia-reperfusion (IR) is being researched. The aim of this study was to shed some light on the molecular background of the protective activity of sitagliptin during hepatic IR. The expression and/or concentration of inflammation and oxidative stress-involved factors have been determined in rat liver homogenates using quantitative RT-PCR and Luminex® xMAP® technology and markers of nitrative and halogenative stress were quantified using targeted metabolomics (LC-MS/MS). Animals (n = 36) divided into four groups were treated with sitagliptin (5 mg/kg) (S and SIR) or saline solution (C and IR), and the livers from IR and SIR were subjected to ischemia (60 min) and reperfusion (24 h). The midkine expression (by 2.2-fold) and the free 3-nitrotyrosine (by 2.5-fold) and IL-10 (by 2-fold) concentration were significantly higher and the Nox4 expression was lower (by 9.4-fold) in the IR than the C animals. As compared to IR, the SIR animals had a lower expression of interleukin-6 (by 4.2-fold) and midkine (by 2-fold), a lower concentration of 3-nitrotyrosine (by 2.5-fold) and a higher Nox4 (by 2.9-fold) and 3-bromotyrosine (by 1.4-fold). In conclusion, IR disturbs the oxidative, nitrative and halogenative balance and aggravates the inflammatory response in the liver, which can be attenuated by low doses of sitagliptin. [ABSTRACT FROM AUTHOR]

Aging is associated with a general decline of cognitive functions, and it is widely accepted that this decline results from changes in the expression of proteins involved in regulation of synaptic plasticity. However, several lines of evidence have accumulated that suggest that the impaired function of the aged brain may be related to significant alterations in the energy metabolism. In the current study, we employed the label-free "Total protein approach" (TPA) method to focus on the similarities and differences in energy metabolism proteomes of young (1-month-old) and aged (22-month-old) murine brains. We quantified over 7000 proteins in each of the following three analyzed brain structures: the hippocampus, the cerebral cortex and the cerebellum. To the best of our knowledge, this is the most extensive quantitative proteomic description of energy metabolism pathways during the physiological aging of mice. The analysis demonstrates that aging does not significantly affect the abundance of total proteins in the studied brain structures, however, the levels of proteins constituting energy metabolism pathways differ significantly between young and aged mice. [ABSTRACT FROM AUTHOR]

Four recombinant (r) allergens (rAmb a 8.0101, rArt v 4.0101, rBet v 2.0101, and rPhl p 12.0101) were successfully produced and used for sensitization studies. The allergens belong to the profilin family which is one of the most numerous allergen families. These four proteins represent allergens originating from pollen of weeds (rAmb a 8.0101 and rArt v 4.0101), tree (rBet v 2.0101) and grass (rPhl p 12.0101). The recombinant allergens were characterized using various biochemical and biophysical methods and tested for their ability to bind patient-derived antibodies. One hundred patients aged 2 to 50 years sensitized to pollen and plant-derived food allergens (IgE > 0.35 kU/L) were included. Sensitization to individual allergen sources and components of birch and timothy pollens was evaluated using multiparameter immunoblots. The presence of IgE to pollen-derived recombinant profilins rAmb a 8.0101, rArt v 4.0101, rBet v 2.0101, and rPhl p 12.0101 in serum was evaluated using ELISA method. The presence of IgE against pollen profilins was detected in 20 out of 100 studied patients. High correlation was seen between IgE ELISA results with individual pollen profilins. In summary, it was shown that the recombinant versions of the four allergenic profilins can be used for sensitization studies and for component-resolved allergy diagnostics. [ABSTRACT FROM AUTHOR]

Introduction: Airway hyperresponsiveness (AHR) is a cardinal feature of asthma. Asthma is a heterogenous disorder which consists of different phenotypes and endotypes. Mechanisms leading to AHR may differ in different asthma subtypes. Allergy to perennial allergens, including house dust mites (HDM) is a major risk factor for asthma development. The aim of this study was to determine predictors of AHR in a well-characterized population of HDM-allergic patients., Material and Methods: In a retrospective analysis 843 patients with HDM-allergic rhinitis with/without asthma were evaluated. The following parameters were included in the analysis: serum concentration of total (t)- and Dermatophagoides pteronyssinus (Dp)-specific IgE, fractional exhaled nitric oxide concentration (FeNO), lung function tests, bronchial challenge with histamine, age sex, and body mass index (BMI). Linear regression analysis was used to determine predictors of AHR., Results: In a simple linear regression analysis baseline lung function results expressed as either forced expiratory volume in 1 s (FEV1) or maximal expiratory flow at 50% of the forced vital capacity (MEF50), FeNO, tIgE, DpIgE, age and BMI affected AHR. A multiple regression analysis demonstrated that in the whole group of HDM-allergic patients the most important, independent predictors of AHR were MEF50, FeNO and DpIgE., Conclusion: Even in a well-characterized asthma phenotype several processes participate in development of AHR. Major, independent predictors of AHR: lung function parameters, FeNO and DpIgE indicate possible targets for therapeutic intervention in a population of HDM-allergic patients.