bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective Role of Natural and Semi-Synthetic Tocopherols on TNFα-Induced ROS Production and ICAM-1 and Cl-2 Expression in HT29 Intestinal Epithelial Cells
Authors: Domazetovic Vladana , Falsetti Irene , Viglianisi Caterina , Vasa Kristian , Aurilia Cinzia , Stio Maria , Menichetti Stefano , Iantomasi Teresa
Published: January 2021

Vitamin E, a fat-soluble compound, possesses both antioxidant and non-antioxidant properties. In this study we evaluated, in intestinal HT29 cells, the role of natural tocopherols, α-Toc and δ-Toc, and two semi-synthetic derivatives, namely bis-δ-Toc sulfide (δ-Toc)2S and bis-δ-Toc disulfide (δ-Toc)2S2, on TNFα-induced oxidative stress, and intercellular adhesion molecule-1 (ICAM-1) and claudin-2 (Cl-2) expression. The role of tocopherols was compared to that of N-acetylcysteine (NAC), an antioxidant precursor of glutathione synthesis. The results show that all tocopherol containing derivatives used, prevented TNFα-induced oxidative stress and the increase of ICAM-1 and Cl-2 expression, and that (δ-Toc)2S and (δ-Toc)2S2 are more effective than δ-Toc and α-Toc. The beneficial effects demonstrated were due to tocopherol antioxidant properties, but suppression of TNFα-induced Cl-2 expression seems not only to be related with antioxidant ability. Indeed, while ICAM-1 expression is strongly related to the intracellular redox state, Cl-2 expression is TNFα-up-regulated by both redox and non-redox dependent mechanisms. Since ICAM-1 and Cl-2 increase intestinal bowel diseases, and cause excessive recruitment of immune cells and alteration of the intestinal barrier, natural and, above all, semi-synthetic tocopherols may have a potential role as a therapeutic support against intestinal chronic inflammation, in which TNFα represents an important proinflammatory mediator.
Depleted Myocardial Coenzyme Q10 in Cavalier King Charles Spaniels with Congestive Heart Failure Due to Myxomatous Mitral Valve Disease
Authors: Christiansen Liselotte B. , Reimann Maria J. , Schou-Pedersen Anne Marie V. , Larsen Steen , Lykkesfeldt Jens , Olsen Lisbeth H.
Published: January 2021

Congestive heart failure (CHF) has been associated with depleted myocardial coenzyme Q10 (Q10) concentrations in human patients. The aim of this study was to investigate associations between myocardial Q10 concentrations and myxomatous mitral valve disease (MMVD) severity in dogs. Furthermore, citrate synthase (CS) activity was analysed to determine if a reduction in myocardial Q10 was associated with mitochondrial depletion in the myocardium. Thirty Cavalier King Charles spaniels (CKCS) in MMVD stages B1 (n = 11), B2 (n = 5) and C (n = 14) according to the American College of Veterinary Internal Medicine (ACVIM) guidelines and 10 control (CON) dogs of other breeds were included. Myocardial Q10 concentration was analysed in left ventricular tissue samples using HPLC-ECD. CKCS with congestive heart failure (CHF; group C) had significantly reduced Q10 concentrations (median, 1.54 µg/mg; IQR, 1.36–1.94), compared to B1 (2.76 µg/mg; 2.10–4.81, p < 0.0018), B2 (3.85 µg/mg; 3.13–4.46, p < 0.0054) and CON dogs (2.8 µg/mg; 1.64–4.88, p < 0.0089). CS activity was comparable between disease groups. In conclusion, dogs with CHF due to MMVD had reduced myocardial Q10 concentrations. Studies evaluating antioxidant defense mechanisms as a therapeutic target for treatment of CHF in dogs are warranted.
Mitochondria-Targeted Antioxidants MitoQ and MitoTEMPO Do Not Influence BRAF-Driven Malignant Melanoma and KRAS-Driven Lung Cancer Progression in Mice
Authors: Le Gal Kristell , Wiel Clotilde , Ibrahim Mohamed X. , Henricsson Marcus , Sayin Volkan I. , Bergo Martin O.
Published: January 2021

Cancer cells produce high levels of mitochondria-associated reactive oxygen species (ROS) that can damage macromolecules, but also promote cell signaling and proliferation. Therefore, mitochondria-targeted antioxidants have been suggested to be useful in anti-cancer therapy, but no studies have convincingly addressed this question. Here, we administered the mitochondria-targeted antioxidants MitoQ and MitoTEMPO to mice with BRAF-induced malignant melanoma and KRAS-induced lung cancer, and found that these compounds had no impact on the number of primary tumors and metastases; and did not influence mitochondrial and nuclear DNA damage levels. Moreover, MitoQ and MitoTEMPO did not influence proliferation of human melanoma and lung cancer cell lines. MitoQ and its control substance dTPP, but not MitoTEMPO, increased glycolytic rates and reduced respiration in melanoma cells; whereas only dTPP produced this effect in lung cancer cells. Our results do not support the use of mitochondria-targeted antioxidants for anti-cancer monotherapy, at least not in malignant melanoma and lung cancer.
Reevaluation of Serum Arylesterase Activity in Neurodevelopmental Disorders
Authors: Piras Ignazio Stefano , Gabriele Stefano , Altieri Laura , Lombardi Federica , Sacco Roberto , Lintas Carla , Manzi Barbara , Curatolo Paolo , Nobile Maria , Rigoletto Catia , Molteni Massimo , Persico Antonio M.
Published: January 2021

Organophosphate compounds (OPs) interfere with neurodevelopment and are neurotoxic for humans and animals. They are first biotransformed to the more toxic oxon form, and then hydrolyzed to specific metabolites by the enzyme paraoxonase/arylesterase, encoded by the gene PON1 located on human chr. 7q21.3. In autism spectrum disorder (ASD) and in attention-deficit/hyperactivity disorder (ADHD), a correlation between OP exposure and disease onset has been reported. In this case-control study, we aimed to replicate our previous work showing reduced levels of serum PON1 arylesterase activity in Italian and Caucasian-American ASD samples, and to extend our analysis to other neurodevelopmental disorders, namely ADHD and developmental language disorder (DLD), also known as specific language impairment (SLI). The arylesterase activity, measured using standard spectrophotometric methods, is significantly reduced in the ADHD, and not in the ASD sample compared with the controls. Our previous results seemingly stem from spuriously high arylesterase levels in the former control sample. Finally, genotyping SNPs rs705379 and rs662 using TDI-FP, a significant effect of rs705379 alleles on the serum arylesterase activity is observed in all of the subgroups tested, regardless of diagnosis, as well as a lack of association between PON1 gene polymorphisms and ASD/ADHD susceptibility in the Italian population. In summary, the serum arylesterase activity is reduced in children and adolescents with ADHD, and this reduction is not due to the functional PON1 gene variants assessed in this study. Based on previous literature, it may more likely reflect enhanced oxidative stress than specific genetic underpinnings.
Influence of Sex and Acute Beetroot Juice Supplementation on 2 KM Running Performance
Authors: Casado Arturo , Domínguez Raúl , Fernandes da Silva Sandro , Bailey Stephen J.
Published: January 2021

Purpose: To assess the effect of acute nitrate-rich (BJ) and nitrate-depleted (PL) beetroot juice ingestion on 2 km running performance in amateur runners, and to what extent the ergogenic effect of BJ supplementation would be influenced by the sex of the participants; Methods: Twenty-four amateur long-distance runners (14 males and 10 females) performed a 2 km time trial (TT) on an outdoor athletics track 2.5 h after ingesting either 140 mL of BJ (~12.8 mmol NO3−) or PL. After the tests, blood [lactate] and ratings of perceived exertion (RPE) related to the leg muscles (RPEmuscular), cardiovascular system (RPEcardio) and general overall RPE (RPEgeneral) were assessed; Results: Compared to PL, BJ supplementation improved 2 km TT performance in both males (p < 0.05) with no supplement × sex interaction effect (p > 0.05). This improvement in 2 km running performance was a function of improved performance in the second 1 km split time in both males and females (p < 0.05). Supplementation with BJ did not alter post-exercise blood [lactate] (p > 0.05) but lowered RPEgeneral (p < 0.05); Conclusions: acute BJ supplementation improves 2 km running performance in amateur runners by enhancing performance over the second half of the TT and lowering RPEgeneral by a comparable magnitude in males and females.
Erratum: Kim, B.-R., et al. A Study on Flow Characteristics and Flow Uniformity for the Efficient Design of a Flow Frame in a Redox Flow Battery. Appl. Sci. 2020, 10, 929
Authors:   Applied Sciences Editorial Office
Published: January 2021

We wish to make the following corrections to the published paper [...]
Power Efficiency Improvement of a Boost Converter Using a Coupled Inductor with a Fuzzy Logic Controller: Application to a Photovoltaic System
Authors: Abouchabana Nabil , Haddadi Mourad , Rabhi Abdelhamid , Grasso Alfio Dario , Tina Giuseppe Marco
Published: January 2021

DC/DC converters are widely used in photovoltaic (PV) systems to track the maximum power points (MPP) of a photovoltaic generator (PVG). The variation of solar radiation (G) and PV cells temperature (T) affect the power efficiency of these DC/DC converters because they change the MPP, thus a sizing adaptation of the component values in these DC/DC converters is needed. Power loss in the inductor due to core saturation can severely degrade power efficiency. This paper proposes a new method that allows to adapt the inductor values according to the variable output power of the PV array in order to minimize losses and improve the converter power efficiency. The main idea is to replace the DC/DC inductor with a coupled inductor where the DC/DC inductor value is adjusted through an additional winding in the magnetic core that modulates the magnetic field inside it. Low current intensities from the PVG supply this winding through a circuit controlled by a fuzzy logic controller in order to regulate the second winding current intensity. Experimental results show a significant improvement of the power efficiency of the proposed solution as compared to a conventional converter.
A Novel Disruptive Innovation-Like Algorithm for Single-Machine Scheduling with Sequence-Dependent Family Setup Times
Authors: Chen Chun-Lung
Published: January 2021

This paper proposes a novel disruptive innovation-like algorithm (DILA) for the problem of scheduling a single machine with sequence-dependent family setup times to minimize the total tardiness. The proposed algorithm is derived from Christensen’s (1997) theory of disruptive innovation. Based on this theory, a DILA is proposed, which first generates two initial populations: the mainstream market population and the emerging market population. Then, to improve the quality of solutions in the populations, three phases are created within a generation. Finally, the DILA allows the populations to evolve for several generations until the termination condition is met. Two populations constructed in DILA are to overcome the weakness of premature. In addition, two functions—the member-added function and member-removed function—implemented in DILA are added to increase the diversity. The DILA was tested on a dataset of 1440 observations from the literature. The computational results confirm that DILA is very effective.
SADG: Self-Aligned Dual NIR-VIS Generation for Heterogeneous Face Recognition
Authors: Zhao Pengcheng , Zhang Fuping , Wei Jianming , Zhou Yingbo , Wei Xiao
Published: January 2021

Heterogeneous face recognition (HFR) has aroused significant interest in recent years, with some challenging tasks such as misalignment problems and limited HFR data. Misalignment occurs among different modalities’ images mainly because of misaligned semantics. Although recent methods have attempted to settle the low-shot problem, they suffer from the misalignment problem between paired near infrared (NIR) and visible (VIS) images. Misalignment can bring performance degradation to most image-to-image translation networks. In this work, we propose a self-aligned dual generation (SADG) architecture for generating semantics-aligned pairwise NIR-VIS images with the same identity, but without the additional guidance of external information learning. Specifically, we propose a self-aligned generator to align the data distributions between two modalities. Then, we present a multiscale patch discriminator to get high quality images. Furthermore, we raise the mean landmark distance (MLD) to test the alignment performance between NIR and VIS images with the same identity. Extensive experiments and an ablation study of SADG on three public datasets show significant alignment performance and recognition results. Specifically, the Rank1 accuracy achieved was close to 99.9% for the CASIA NIR-VIS 2.0, Oulu-CASIA NIR-VIS and BUAA VIS-NIR datasets, respectively.
Conversion of Glucose to 5-Hydroxymethylfurfural, Levulinic Acid, and Formic Acid in 1,3-Dibutyl-2-(2-butoxyphenyl)-4,5-diphenylimidazolium Iodide-Based Ionic Liquid
Authors: Zunita Megawati , Wahyuningrum Deana , Buchari  , Bundjali Bunbun , Wenten I Gede , Boopathy Ramaraj
Published: January 2021

The separation process between 5-hydroxymethylfurfural (HMF) and trace glucose in glucose conversion is important in the biphasic system (aqueous–organic phase), due to the partial solubility property of HMF in water. In addition, the yield of HMF via the dehydration reaction of glucose in water is low (under 50%) with the use of Brønsted acid as a catalyst. Therefore, this study was conducted to optimize the production and separation of products by using a new hydrophobic ionic liquid (IL), which is more selective than water. The new IL (1,3-dibutyl-2-(2-butoxyphenyl)-4,5-diphenyl imidazolium iodide) [DBDIm]I was used as a solvent and was optimized for the dehydration reaction of glucose to make a more selective separation of HMF, levulinic acid (LA), and formic acid (FA). [DBDIm]I showed high performance as a solvent for glucose conversion at 100 °C for 120 min, with a yield of 82.2% HMF, 14.9% LA, and 2.9% FA in the presence of sulfuric acid as the Brønsted acid catalyst.
Modified Levy Flight Optimization for a Maximum Power Point Tracking Algorithm under Partial Shading
Authors: Charin Chanuri , Ishak Dahaman , Mohd Zainuri Muhammad Ammirrul Atiqi , Ismail Baharuddin
Published: January 2021

This paper presents a novel modified Levy flight optimization for a photovoltaic PV solar energy system. Conventionally, the Perturb and Observe (P&O) algorithm has been widely deployed in most applications due to its simplicity and ease of implementation. However, P&O suffers from steady-state oscillation and stability, besides its failure in tracking the optimum power under partial shading conditions and fast irradiance changes. Therefore, a modified Levy flight optimization is proposed by incorporating a global search of beta parameters, which can significantly improve the tracking capability in local and global searches compared to the conventional methods. The proposed modified Levy flight optimization is verified with simulations and experiments under uniform, non-uniform, and dynamic conditions. All results prove the advantages of the proposed modified Levy flight optimization in extracting the optimal power with a fast response and high efficiency from the PV arrays.
Dynamic Railway Derailment Risk Analysis with Text-Data-Based Bayesian Network
Authors: Yang Liu , Li Keping , Song Guozheng , Khan Faisal
Published: January 2021

In recent years, transportation system safety analysis has become increasingly challenging and highly demanding. Unstructured data contain sufficient information from which inherent interactions can be extracted. Determining how to process and fuse a large amount of unstructured data is a challenging task. In this paper, we propose a text-based Bayesian network (TBN) method to establish a Bayesian network (BN) based on text records, where the BN’s arcs are obtained from barrier relationships identified by a graphical model and its prior probabilities stem from fault trees. The comparative experimental results illustrate that the text-based method in TBN is efficient. The precision, recall and F-measure of TBN are 8.64%, 10.70% and 9.84% higher, respectively, than the most frequent (MF) result. Moreover, compared to the traditional BN, whose prior probabilities are frequently acquired from experts, the prior probabilities of the proposed text-based BN (TBN) have a high confidence. The experimental results of a train derailment accident case study show that with changes in the train derailment probabilities and the safety potentials of the barriers, the TBN generates quantitative results and reveals the critical risks of derailment accidents. Additionally, this work demonstrates relevant nonlinear relationships to improve the assessment results. Therefore, based on text-based data, this study reveals that barrier safety analysis has the potential to identify high-risk barriers, which can guide managers to enhance these barriers.
Anticipatory Troubleshooting
Authors: Hasidi Netanel , Kalech Meir
Published: January 2021

Troubleshooting is the process of diagnosing and repairing a system that is behaving abnormally. It involves performing various diagnostic and repair actions. Performing these actions may incur costs, and traditional troubleshooting algorithms aim to minimize the costs incurred until the system is fixed. Prognosis deals with predicting future failures. We propose to incorporate prognosis and diagnosis techniques to solve troubleshooting problems. This integration enables (1) better fault isolation and (2) more intelligent decision making with respect to the repair actions to employ to minimize troubleshooting costs over time. In particular, we consider an anticipatory troubleshooting challenge in which we aim to minimize the costs incurred to fix the system over time, while reasoning about both current and future failures. Anticipatory troubleshooting raises two main dilemmas: the fix–replace dilemma and the replace-healthy dilemma. The fix–replace dilemma is the question of how to repair a faulty component: fixing it or replacing it with a new one. The replace-healthy dilemma is the question of whether a healthy component should be replaced with a new one in order to prevent it from failing in the future. We propose to solve these dilemmas by modeling them as a Markov decision problem and reasoning about future failures using techniques from the survival analysis literature. The resulting algorithm was evaluated experimentally, showing that the proposed anticipatory troubleshooting algorithms yield lower overall costs compared to troubleshooting algorithms that do not reason about future faults.
ABACO: A New Model of Microalgae-Bacteria Consortia for Biological Treatment of Wastewaters
Authors: Sánchez-Zurano Ana , Rodríguez-Miranda Enrique , Guzmán José Luis , Acién-Fernández Francisco Gabriel , Fernández-Sevilla José M. , Molina Grima Emilio
Published: January 2021

Microalgae-bacteria consortia have been proposed as alternatives to conventional biological processes to treat different types of wastewaters, including animal slurry. In this work, a microalgae-bacteria consortia (ABACO) model for wastewater treatment is proposed, it being calibrated and validated using pig slurry. The model includes the most relevant features of microalgae, such as light dependence, endogenous respiration, and growth and nutrient consumption as a function of nutrient availability (especially inorganic carbon), in addition to the already reported features of heterotrophic and nitrifying bacteria. The interrelation between the different populations is also included in the model, in addition to the simultaneous release and consumption of the most relevant compounds, such as oxygen and carbon dioxide. The implementation of the model has been performed in MATLAB software; the calibration of model parameters was carried out using genetic algorithms. The ABACO model allows one to simulate the dynamics of different components in the system, and the relative proportions of microalgae, heterotrophic bacteria, and nitrifying bacteria. The percentage of each microbial population obtained with the model was confirmed by respirometric techniques. The proposed model is a powerful tool for the development of microalgae-related wastewater treatment processes, both to maximize the production of microalgal biomass and to optimize the wastewater treatment capacity.
Inductive Thermography as Non-Destructive Testing for Railway Rails
Authors: Tuschl Christoph , Oswald-Tranta Beate , Eck Sven
Published: January 2021

Inductive thermography is a non-destructive testing method, whereby the specimen is slightly heated with a short heating pulse (0.1–1 s) and the temperature change on the surface is recorded with an infrared (IR) camera. Eddy current is induced by means of high frequency (HF) magnetic field in the surface ‘skin’ of the specimen. Since surface cracks disturb the eddy current distribution and the heat diffusion, they become visible in the IR images. Head checks and squats are specific types of damage in railway rails related to rolling contact fatigue (RCF). Inductive thermography can be excellently used to detect head checks and squats on rails, and the method is also applicable for characterizing individual cracks as well as crack networks. Several rail pieces with head checks, with artificial electrical discharge-machining (EDM)-cuts and with a squat defect were inspected using inductive thermography. Aiming towards rail inspection of the track, 1 m long rail pieces were inspected in two different ways: first via a ‘stop-and-go’ technique, through which their subsequent images are merged together into a panorama image, and secondly via scanning during a continuous movement of the rail. The advantages and disadvantages of both methods are compared and analyzed. Special image processing tools were developed to automatically fully characterize the rail defects (average crack angle, distance between cracks and average crack length) in the recorded IR images. Additionally, finite element simulations were used to investigate the effect of the measurement setup and of the crack parameters, in order to optimize the experiments.
Fundamental Parameters Related to Selenium Kα and Kβ Emission X-ray Spectra
Authors: Guerra Mauro , Sampaio Jorge M. , Vília Gonçalo R. , Godinho César A. , Pinheiro Daniel , Amaro Pedro , Marques José P. , Machado Jorge , Indelicato Paul , Parente Fernando , Santos José Paulo
Published: January 2021

We present relativistic ab initio calculations of fundamental parameters for atomic selenium, based on the Multiconfiguration Dirac-Fock method. In detail, fluorescence yields and subshell linewidths, both of K shell, as well as Kβ to Kα intensity ratio are provided, showing overall agreement with previous theoretical calculations and experimental values. Relative intensities were evaluated assuming the same ionization cross-section for the K-shell hole states, leading to a statistical distribution of these initial states. A method for estimating theoretical linewidths of X-ray lines, where the lines are composed by a multiplet of fine-structure levels that are spread in energy, is proposed. This method provides results that are closer to Kα1,2 experimental width values than the usual method, although slightly higher discrepancies occur for the Kβ1,3 lines. This indicates some inaccuracies in the calculation of Auger rates that have a higher contribution for partial linewidths of the subshells involved in the Kβ1,3 profile. Apart from this, the calculated value of Kβ to Kα intensity ratio, which is less sensitive to Auger rates issues, is in excellent agreement with recommended values.
Modulation of the Tissue Expression Pattern of Zebrafish CRP-Like Molecules Suggests a Relevant Antiviral Role in Fish Skin
Authors: Bello-Perez Melissa , Adamek Mikolaj , Coll Julio , Figueras Antonio , Novoa Beatriz , Falco Alberto
Published: January 2021

Recent studies suggest that short pentraxins in fish might serve as biomarkers for not only bacterial infections, as in higher vertebrates including humans, but also for viral ones. These fish orthologs of mammalian short pentraxins are currently attracting interest because of their newly discovered antiviral activity. In the present work, the modulation of the gene expression of all zebrafish short pentraxins (CRP-like proteins, CRP1-7) was extensively analyzed by quantitative polymerase chain reaction. Initially, the tissue distribution of crp1-7 transcripts and how the transcripts varied in response to a bath infection with the spring viremia of carp virus, were determined. The expression of crp1-7 was widely distributed and generally increased after infection (mostly at 5 days post infection), except for crp1 (downregulated). Interestingly, several crp transcription levels significantly increased in skin. Further assays in mutant zebrafish of recombinant activation gene 1 (rag1) showed that all crps (except for crp2, downregulated) were already constitutively highly expressed in skin from rag1 knockouts and only increased moderately after viral infection. Similar results were obtained for most mx isoforms (a reporter gene of the interferon response), suggesting a general overcompensation of the innate immunity in the absence of the adaptive one.
Metabolic Regulation of Ferroptosis in Cancer
Authors: Kim Min Ji , Yun Greg Jiho , Kim Sung Eun
Published: January 2021

Ferroptosis is a unique cell death mechanism that is executed by the excessive accumulation of lipid peroxidation in cells. The relevance of ferroptosis in multiple human diseases such as neurodegeneration, organ damage, and cancer is becoming increasingly evident. As ferroptosis is deeply intertwined with metabolic pathways such as iron, cyst(e)ine, glutathione, and lipid metabolism, a better understanding of how ferroptosis is regulated by these pathways will enable the precise utilization or prevention of ferroptosis for therapeutic uses. In this review, we present an update of the mechanisms underlying diverse metabolic pathways that can regulate ferroptosis in cancer.
Isolation and Characterization of Fungal Endophytes Isolated from Medicinal Plant Ephedra pachyclada as Plant Growth-Promoting
Authors: Khalil Ahmed Mohamed Aly , Hassan Saad El-Din , Alsharif Sultan M. , Eid Ahmed M. , Ewais Emad El-Din , Azab Ehab , Gobouri Adil A. , Elkelish Amr , Fouda Amr
Published: January 2021

Endophytic fungi are widely present in internal plant tissues and provide different benefits to their host. Medicinal plants have unexplored diversity of functional fungal association; therefore, this study aimed to isolate endophytic fungi associated with leaves of medicinal plants Ephedra pachyclada and evaluate their plant growth-promoting properties. Fifteen isolated fungal endophytes belonging to Ascomycota, with three different genera, Penicillium, Alternaria, and Aspergillus, were obtained from healthy leaves of E. pachyclada. These fungal endophytes have varied antimicrobial activity against human pathogenic microbes and produce ammonia and indole acetic acid (IAA), in addition to their enzymatic activity. The results showed that Penicillium commune EP-5 had a maximum IAA productivity of 192.1 ± 4.04 µg mL−1 in the presence of 5 µg mL−1 tryptophan. The fungal isolates of Penicillium crustosum EP-2, Penicillium chrysogenum EP-3, and Aspergillus flavus EP-14 exhibited variable efficiency for solubilizing phosphate salts. Five representative fungal endophytes of Penicillium crustosum EP-2, Penicillium commune EP-5, Penicillium caseifulvum EP-11, Alternaria tenuissima EP-13, and Aspergillus flavus EP-14 and their consortium were selected and applied as bioinoculant to maize plants. The results showed that Penicillium commune EP-5 increased root lengths from 15.8 ± 0.8 to 22.1 ± 0.6. Moreover, the vegetative growth features of inoculated maize plants improved more than the uninoculated ones.
Clinical Phenotypes of Parkinson’s Disease Associate with Distinct Gut Microbiota and Metabolome Enterotypes
Authors: Vascellari Sarah , Melis Marta , Palmas Vanessa , Pisanu Silvia , Serra Alessandra , Perra Daniela , Santoru Maria Laura , Oppo Valentina , Cusano Roberto , Uva Paolo , Atzori Luigi , Morelli Micaela , Cossu Giovanni , Manzin Aldo
Published: January 2021

Parkinson’s disease (PD) is a clinically heterogenic disorder characterized by distinct clinical entities. Most studies on motor deficits dichotomize PD into tremor dominant (TD) or non-tremor dominant (non-TD) with akinetic-rigid features (AR). Different pathophysiological mechanisms may affect the onset of motor manifestations. Recent studies have suggested that gut microbes may be involved in PD pathogenesis. The aim of this study was to investigate the gut microbiota and metabolome composition in PD patients in relation to TD and non-TD phenotypes. In order to address this issue, gut microbiota and the metabolome structure of PD patients were determined from faecal samples using 16S next generation sequencing and gas chromatography–mass spectrometry approaches. The results showed a reduction in the relative abundance of Lachnospiraceae, Blautia, Coprococcus, Lachnospira, and an increase in Enterobacteriaceae, Escherichia and Serratia linked to non-TD subtypes. Moreover, the levels of important molecules (i.e., nicotinic acid, cadaverine, glucuronic acid) were altered in relation to the severity of phenotype. We hypothesize that the microbiota/metabolome enterotypes associated to non-TD subtypes may favor the development of gut inflammatory environment and gastrointestinal dysfunctions and therefore a more severe α-synucleinopathy. This study adds important information to PD pathogenesis and emphasizes the potential pathophysiological link between gut microbiota/metabolites and PD motor subtypes.
The Structural Properties of Odorants Modulate Their Association to Human Odorant Binding Protein
Authors: Castro Tarsila G. , Silva Carla , Matamá Teresa , Cavaco-Paulo Artur
Published: January 2021

The binding of known odorant molecules to the human odorant-binding protein (hOBP) was evaluated in silico. Docking experiments elucidate the preferable binding site and binding affinity of odorant molecules to hOBP. The physicochemical properties molecular weight (MW), vapor pressure (Vp), hydrophobicity level (logP), number of double bonds (NºDB), degree of unsaturation (DoU) and the chemical classification, were selected for the study of odorant modulation. Here, these properties were analyzed concerning 30 pleasant and 30 unpleasant odorants, chosen to represent a wide variety of compounds and to determine their influence on the binding energy to hOBP. Our findings indicate that MW, logP and Vp are the most important odorant variables, directly correlated to odorant-binding energies (ΔGbinding) towards hOBP. Understanding how the odorants behave when complexed with the OBP in human olfaction opens new possibilities for the development of future biotechnological applications, including sensory devices, medical diagnosis, among others.
Breast Cancer-Derived Microvesicles Are the Source of Functional Metabolic Enzymes as Potential Targets for Cancer Therapy
Authors: Risha Yousef , Susevski Vanessa , Hüttmann Nico , Poolsup Suttinee , Minic Zoran , Berezovski Maxim V.
Published: January 2021

Membrane-derived extracellular vesicles, referred to as microvesicles (MVs), have been proposed to participate in several cancer diseases. In this study, MV fractions were isolated by differential ultracentrifugation from a metastatic breast cancer (BC) cell line MDA-MB-231 and a non-cancerous breast cell line MCF10A, then analyzed by nano-liquid chromatography coupled to tandem mass spectrometry. A total of 1519 MV proteins were identified from both cell lines. The data obtained were compared to previously analyzed proteins from small extracellular vesicles (sEVs), revealing 1272 proteins present in both MVs and sEVs derived from the MDA-MB-231 cell line. Among the 89 proteins unique to MDA-MB-231 MVs, three enzymes: ornithine aminotransferase (OAT), transaldolase (TALDO1) and bleomycin hydrolase (BLMH) were previously proposed as cancer therapy targets. These proteins were enzymatically validated in cells, sEVs, and MVs derived from both cell lines. The specific activity of OAT and TALDO1 was significantly higher in MDA-MB-231-derived MVs than in MCF10A MVs. BLMH was highly expressed in MDA-MB-231-derived MVs, compared to MCF10A MVs. This study shows that MVs carry functional metabolic enzymes and provides a framework for future studies of their biological role in BC and potential in therapeutic applications.
Dopamine in Health and Disease: Much More Than a Neurotransmitter
Authors: Franco Rafael , Reyes-Resina Irene , Navarro Gemma
Published: January 2021

Dopamine is derived from an amino acid, phenylalanine, which must be obtained through the diet. Dopamine, known primarily to be a neurotransmitter involved in almost any higher executive action, acts through five types of G-protein-coupled receptors. Dopamine has been studied extensively for its neuronal handling, synaptic actions, and in relation to Parkinson’s disease. However, dopamine receptors can be found extra-synaptically and, in addition, they are not only expressed in neurons, but in many types of mammalian cells, inside and outside the central nervous system (CNS). Recent studies show a dopamine link between the gut and the CNS; the mechanisms are unknown, but they probably require cells to act as mediators and the involvement of the immune system. In fact, dopamine receptors are expressed in almost any cell of the immune system where dopamine regulates various processes, such as antigen presentation, T-cell activation, and inflammation. This likely immune cell-mediated linkage opens up a new perspective for the use of dopamine-related drugs, i.e., agonist–antagonist–allosteric modulators of dopamine receptors, in a variety of diseases.
Acknowledgment to Reviewers of Brain Sciences in 2020
Authors:   Brain Sciences Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Brain Sciences maintains its standards for the high quality of its published papers [...]
Obsessive-Compulsive Disorder and Decision Making under Ambiguity: A Systematic Review with Meta-Analysis
Authors: Nisticò Veronica , De Angelis Andrea , Erro Roberto , Demartini Benedetta , Ricciardi Lucia
Published: January 2021

In the last decade, decision-making has been proposed to have a central role in obsessive-compulsive disorder (OCD) aetiology, since patients show pathological doubt and an apparent inability to make decisions. Here, we aimed to comprehensively review decision making under ambiguity, as measured by the Iowa Gambling Task (IGT), in OCD, using a meta-analytic approach. According to PRISMA Guidelines, we selected 26 studies for a systematic review and, amongst them, 16 studies were included in a meta-analysis, comprising a total of 846 OCD patients and 763 healthy controls (HC). Our results show that OCD patients perform significantly lower than HC at the IGT, pointing towards the direction of a decision making impairment. In particular, this deficit seems to emerge mainly in the last three blocks of the IGT. IGT scores in OCD patients under the age of 18 were still significantly lower than in HC. Finally, no difference emerged between medicated and unmedicated patients, since they both scored significantly lower at the IGT compared to HC. In conclusion, our results are in line with the hypothesis according to which decision making impairment might represent a potential endophenotype lying between the clinical manifestation of OCD and its neurobiological aetiology.
Nociceptive Sensitization by Activation of Protease-Activated Receptor 2 in a Rat Model of Incisional Pain
Authors: Kido Kanta , Katagiri Norika , Kawana Hiromasa , Sugino Shigekazu , Yamauchi Masanori , Masaki Eiji
Published: January 2021

Postoperative pain and consequent inflammatory responses after tissue incision adversely affects many surgical patients due to complicated mechanisms. In this study, we examined whether activation of protease-activated receptor 2 (PAR-2), which is stimulated by tryptase from mast cells, elicits nociception and whether the PAR-2 antagonist could reduce incisional nociceptive responses in vivo and in vitro. The effects of a selective PAR-2 antagonist, N3-methylbutyryl-N-6-aminohexanoyl-piperazine (ENMD-1068), pretreatment on pain behaviors were assessed after plantar incision in rats. The effects of a PAR-2 agonist, SLIGRL-NH2, on nociception was assessed after the injection into the hind paw. Furthermore, the responses of C-mechanosensitive nociceptors to the PAR-2 agonist were observed using an in vitro skin–nerve preparation as well. Intraplantar injection of SLIGRL-NH2 elicited spontaneous nociceptive behavior and hyperalgesia. Local administration of ENMD-1068 suppressed guarding behaviors, mechanical and heat hyperalgesia only within the first few hours after incision. SLIGRL-NH2 caused ongoing activity in 47% of C-mechanonociceptors in vitro. This study suggests that PAR-2 may support early nociception after incision by direct or indirect sensitization of C-fibers in rats. Moreover, PAR-2 may play a regulatory role in the early period of postoperative pain together with other co-factors to that contribute to postoperative pain.
Consecutive Controlled Case Series on Effectiveness of Opipramol in Severe Sleep Bruxism Management—Preliminary Study on New Therapeutic Path
Authors: Wieckiewicz Mieszko , Martynowicz Helena , Wieczorek Tomasz , Wojakowska Anna , Sluzalec-Wieckiewicz Katarzyna , Gac Pawel , Poreba Rafal , Mazur Grzegorz , Winocur Efraim , Smardz Joanna
Published: January 2021

Background: Sleep bruxism (SB) management aims to reduce the number and magnitude of bruxism episodes per hour of a patient’s sleep and, therefore, reduce the potentially negative clinical consequences. Opipramol belongs to the group of tricyclic antidepressants (TCAs) and is considered as an atypical TCA, as it acts primarily as a sigma receptor agonist. This study aimed to preliminarily determine the effectiveness of opipramol in the management of severe SB. Methods: A total of 19 otherwise healthy participants with severe SB diagnosed during stage I video polysomnography (vPSG) were subjected to an 8-week pharmacotherapy trial with a 100 mg bedtime daily dose of opipramol and were then analyzed by control stage II vPSG. Results: The participants included 14 females and 5 males, aged 20–47 years (mean ± standard deviation: 32.32 ± 8.12). A comparison of stage I and II vPSG recordings showed a decrease in all the studied SB parameters in 78.85% of participants. Only in a small group of participants (15.53%) was a non-significant increase of SB parameters observed. Conclusions: A single 100 mg dose of opipramol at bedtime seems to positively affect the reduction of SB in otherwise healthy individuals diagnosed with severe SB. However, the subject requires further research on a larger population including a control group.
A Systematic Review of Executive Function and Information Processing Speed in Major Depression Disorder
Authors: Nuño Laura , Gómez-Benito Juana , Carmona Viviana R. , Pino Oscar
Published: January 2021

Background: Major depression is a psychiatric disorder characterized neuropsychologically by poor performance in tasks of memory, attention, processing speed, and executive function. The aim of this systematic review was to examine the evidence regarding the neuropsychological profile of people with major depression and to determine which of two explanatory models—the processing speed hypothesis or the cognitive effort hypothesis—has most empirical support. Methods: We searched three relevant databases and reviewed the reference lists of the articles retrieved. The results obtained with the Trail Making Test and the Stroop Color-Word Test were reviewed for 37 studies published between 1993 and 2020. Results: The empirical evidence supports both hypotheses: cognitive effort and processing speed, suggesting that depression is not only characterized by psychomotor slowing but also involves a specific deficit in executive function. Discussion: We discuss potentially relevant variables that should be considered in future research in order to improve knowledge about the neurocognitive profile of depression. The main limitation of this study derives from the considerable heterogeneity of participants with MD, which makes it difficult to compare and integrate the data.
Adrenergic Signaling in Immunotherapy of Cancer: Friend or Foe?
Authors: Jensen Agnete Witness Praest , Carnaz Simões Ana Micaela , thor Straten Per , Holmen Olofsson Gitte
Published: January 2021

The incidence of cancer is increasing worldwide, which is to a large extent related to the population’s increasing lifespan. However, lifestyle changes in the Western world are causative as well. Exercise is intrinsically associated with what one could call a “healthy life”, and physical activity is associated with a lower risk of various types of cancer. Mouse models of exercise have shown therapeutic efficacy across numerous cancer models, at least in part due to the secretion of adrenaline, which mobilizes cells of the immune system, i.e., cytotoxic T and natural killer (NK) cells, through signaling of the β-2 adrenergic receptor (β2AR). Clinical trials aiming to investigate the clinical value of exercise are ongoing. Strikingly, however, the use of β-blockers—antagonists of the very same signaling pathway—also shows signs of clinical potential in cancer therapy. Cancer cells also express β-adrenergic receptors (βARs) and signaling of the receptor is oncogenic. Moreover, there are data to suggest that β2AR signaling in T cells renders the cell functionally suppressed. In this paper, we discuss these seemingly opposing mechanisms of cancer therapy—exercise, which leads to increased β2AR signaling, and β-blocker treatment, which antagonizes that same signaling—and suggest potential mechanisms and possibilities for their combination.
COVID-19 and Its Impact on Upper Gastrointestinal (GI) Cancer Management
Authors: Fernando Shalini , Veli Mesel , Mohammadi Borzoueh , Millar Andrew , Khan Khurum
Published: January 2021

Coronavirus disease 2019 (COVID-19), caused by the novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has left dramatic footprints on human health and economy. Cancer, whilst not an infective disease, is prevalent in epidemic proportions and cannot be pretermitted due to the impact of COVID-19. As we emanate from the second national lockdown in the UK with mixed feelings of hope and despair—due to vaccination and new COVID-19 variant, respectively—we reflect on the impact of the first wave on the provision on diagnosis and management of with upper gastrointestinal (UGI) cancers. This review provides a critical analysis of available literature on COVID-19 and its impact on cancer management in general and that of UGI cancers in particular.
Tumor Cells and Cancer-Associated Fibroblasts: An Updated Metabolic Perspective
Authors: Gentric Géraldine , Mechta-Grigoriou Fatima
Published: January 2021

During the past decades, metabolism and redox imbalance have gained considerable attention in the cancer field. In addition to the well-known Warburg effect occurring in tumor cells, numerous other metabolic deregulations have now been reported. Indeed, metabolic reprograming in cancer is much more heterogeneous than initially thought. In particular, a high diversity of carbon sources used by tumor cells has now been shown to contribute to this metabolic heterogeneity in cancer. Moreover, the molecular mechanisms newly highlighted are multiple and shed light on novel actors. Furthermore, the impact of this metabolic heterogeneity on tumor microenvironment has also been an intense subject of research recently. Here, we will describe the new metabolic pathways newly uncovered in tumor cells. We will also have a particular focus on Cancer-Associated Fibroblasts (CAF), whose identity, function and metabolism have been recently under profound investigation. In that sense, we will discuss about the metabolic crosstalk between tumor cells and CAF.
Advances in Nanocarriers for Effective Delivery of Docetaxel in the Treatment of Lung Cancer: An Overview
Authors: A. Razak S. Aishah , Mohd Gazzali Amirah , Fisol Faisalina Ahmad , M. Abdulbaqi Ibrahim , Parumasivam Thaigarajan , Mohtar Noratiqah , A. Wahab Habibah
Published: January 2021

Docetaxel (DCX) is a highly effective chemotherapeutic drug used in the treatment of different types of cancer, including non-small cell lung cancer (NSCLC). The drug is known to have low oral bioavailability due to its low aqueous solubility, poor membrane permeability and susceptibility to hepatic first-pass metabolism. To mitigate these problems, DCX is administered via the intravenous route. Currently, DCX is commercially available as a single vial that contains polysorbate 80 and ethanol to solubilize the poorly soluble drug. However, this formulation causes short- and long-term side effects, including hypersensitivity, febrile neutropenia, fatigue, fluid retention, and peripheral neuropathy. DCX is also a substrate to the drug efflux pump P-glycoprotein (P-gp) that would reduce its concentration within the vicinity of the cells and lead to the development of drug resistance. Hence, the incorporation of DCX into various nanocarrier systems has garnered a significant amount of attention in recent years to overcome these drawbacks. The surfaces of these drug-delivery systems indeed can be functionalized by modification with different ligands for smart targeting towards cancerous cells. This article provides an overview of the latest nanotechnological approaches and the delivery systems that were developed for passive and active delivery of DCX via different routes of administration for the treatment of lung cancer.
A Hepatitis B Virus-Derived Peptide Exerts an Anticancer Effect via TNF/iNOS-producing Dendritic Cells in Tumor-Bearing Mouse Model
Authors: Yang Soo-Bin , Lee Mi-Hyun , Kim Bo-Ram , Choi Yu-Min , Kim Bum-Joon
Published: January 2021

Recently, we reported a 6-mer hepatitis B virus (HBV)-derived peptide, Poly6, that exerts antiviral effects against human immunodeficiency virus type 1 (HIV-1). Here, we explored the immunotherapeutic potential of Poly6 via its administration into dendritic cells (DCs) in a mouse model. Our data revealed that Poly6 treatment led to enhanced production of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS)-producing DCs (Tip-DCs) in a type 1 interferon (IFN-I)-dependent manner via the induction of mitochondrial stress. Poly6 treatment in mice implanted with MC38 cells, a murine colon adenocarcinoma line, led to attenuated tumor formation, primarily due to direct cell death induced by Tip-DC mediated nitric oxide (NO) production and indirect killing by Tip-DC mediated cluster of differentiation 8 (CD8) cytotoxic T lymphocyte (CTL) activation via CD40 activation. Moreover, Poly6 treatment demonstrated an enhanced anticancer effect with one of the checkpoint inhibitors, the anti PD-L1 antibody. In conclusion, our data reveal that Poly6 treatment elicits an antitumor immune response in mice, possibly through NO-mediated oncolytic activity via Tip-DC activation and Tip-DC mediated CTL activation. This suggests that Poly6 represents a potential adjuvant for cancer immunotherapy by enhancing the anticancer effects of immune checkpoint inhibitors.