bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein and Amino Acid Content in Four Brands of Commercial Table Eggs in Retail Markets in Relation to Human Requirements
Authors: Attia Youssef A. , Al-Harthi Mohammed A. , Korish Mohamed A. , Shiboob Mohamed H.
Published: March 2020

Considering the common believe that all eggs in the retail market are nutritionally similar, four different commercial sources of eggs (A, B, C, and D) available in a retail market were collected to investigate the crude protein and amino acid content, as well as the protein quality in the whole edible part of eggs (albumen + yolk), egg albumen, and egg yolk, separately. Five egg samples per source were collected four times during the experimental period, which resulted in a total number of 20 samples that were pooled to finally present five samples per source of eggs. The results show that crude protein in albumen was significantly higher in A and B than that of C and D, but the difference was found among edible parts of eggs such as yolk > whole edible part > albumen. Essential amino acids (arginine, histidine, isoleucine, lysine, methionine, methionine + cysteine, phenylalanine, phenylalanine + tyrosine, threonine, and valine) of eggs significantly differed according to the source of eggs, but eggs from different sources could provide from 17.4–26.7% of recommended daily allowance (RDA) of amino acids for adults. Essential amino acids (EAAs) were higher (p ≤ 0.05) in eggs from sources A and B than in source D, while source C exhibited intermediate values. Source B had greater (p ≤ 0.05) non-essential amino acids (NEAAs) than did sources C and D in whole edible egg, while source A displayed intermediate values. The phenylalanine + tyrosine, histidine, and lysine were the 1st, 2nd, and 3rd limiting amino acids in all sources of eggs. In conclusion, the investigated eggs showed different EAAs/NEAAs ratio and antioxidant amino acids, indicating a potential for enhancing nutritional values and extending the shelf life of eggs by different nutritional additions.
Effects of Acute Heat Stress on a Newly Established Chicken Hepatocyte—Nonparenchymal Cell Co-Culture Model
Authors: Mackei Máté , Molnár Andor , Nagy Szabolcs , Pál László , Kővágó Csaba , Gálfi Péter , Dublecz Károly , Husvéth Ferenc , Neogrády Zsuzsanna , Mátis Gábor
Published: March 2020

Heat stress is one of the most important issues in broiler flocks impairing animal health and productivity. On a cellular level, excess heat exposure can trigger heat shock response acting for the restoration of cell homeostasis by several mechanisms, such as affecting heat shock protein synthesis, redox homeostasis and pro-inflammatory cytokine production. The major aim of this study was to establish a novel avian hepatocyte—nonparenchymal cell co-culture as a model for investigating the cellular effects of heat stress and its interaction with inflammation in chicken liver. Cell fractions were isolated by differential centrifugation from a freshly perfused chicken liver, and hepatocyte mono-cultures as well as hepatocyte–nonparenchymal cell co-cultures (with cell ratio 6:1, hepatocytes to nonparenchymal cells, mimicking a milder hepatic inflammation) were prepared. Isolated and cultured cells were characterized by flow cytometry and immunocytochemistry applying hepatocyte- and macrophage-specific antibodies. Confluent cell cultures were exposed to 43 °C temperature for 1 or 2 h, while controls were cultured at 38.5 °C. The metabolic activity, LDH enzyme activity, reactive oxygen species (H2O2) production, extracellular concentration of heat shock protein 70 (HSP70), and that of the pro-inflammatory cytokines interleukin (IL-)6 and IL-8 were assessed. Shorter heat stress applied for 1 h could strongly influence liver cell function by significantly increasing catabolic metabolism and extracellular H2O2 release, and by significantly decreasing HSP70, IL-6, and IL-8 production on both cell culture models. However, all these alterations were restored after 2 h heat exposure, indicating a fast recovery of liver cells. Hepatocyte mono-cultures and hepatocyte—nonparenchymal cell co-cultures responded to heat stress in a similar manner, but the higher metabolic rate of co-cultured cells may have contributed to a better capability of inflamed liver cells for accommodation to stress conditions. In conclusion, the established new primary cell culture models provide suitable tools for studying the hepatic inflammatory and stress response. The results of this study highlight the impact of short-term heat stress on the liver in chickens, underline the mediatory role of oxidative stress in acute stress response, and suggest a fast cellular adaptation potential in liver cells.
Development of a DSP Microcontroller-Based Fuzzy Logic Controller for Heliostat Orientation Control
Authors: Salgado-Plasencia Eugenio , Carrillo-Serrano Roberto V. , Toledano-Ayala Manuel
Published: March 2020

This paper describes the design and implementation of a heliostat orientation control system based on a low-cost microcontroller. The proposed system uses a fuzzy logic controller (FLC) with the Center of Sums defuzzification method embedded on a dsPIC33EP256MU806 Digital Signal Processor (DSP), in order to modify the orientation of a heliostat by controlling the angular position of two DC motors connected to the axes of the heliostat. The FLC is compared to a traditional Proportional-Integral-Derivative (PID) controller to evaluate the performance of the system. Both the FLC and PID controller were designed for the position control of the heliostat DC motors at no load, and then they were implemented in the orientation control of the heliostat using the same controller parameters. The experimental results show that the FLC has a better performance and flexibility than a traditional PID controller in the orientation control of a heliostat.
Using the Equivalent Material Concept and the Average Strain Energy Density to Analyse the Fracture Behaviour of Structural Materials
Authors: Cicero Sergio , Fuentes Juan Diego , Torabi Ali Reza
Published: March 2020

This paper provides a complete overview of the applicability of the Equivalent Material Concept in conjunction with the Average Strain Energy Density criterion, to provide predictions of fracture loads in structural materials containing U-notches. The Average Strain Density Criterion (ASED) has a linear-elastic nature, so in principle, it does not provide satisfactory predictions of fracture loads in those materials with nonlinear behaviour. However, the Equivalent Material Concept (EMC) is able to transform a physically nonlinear material into an equivalent linear-elastic one and, therefore, the combination of the ASED criterion with the EMC (EMC–ASED criterion) should provide good predictions of fracture loads in physically nonlinear materials. The EMC–ASED criterion is here applied to different types of materials (polymers, composites and metals) with different grades of nonlinearity, showing the accuracy of the corresponding fracture load predictions and revealing qualitatively the limitations of the methodology. It is shown how the EMC–ASED criterion provides good predictions of fracture loads in nonlinear materials as long as the nonlinear behaviour is mainly limited to the tensile behaviour, and how the accuracy decreases when the nonlinear behaviour is extended to the material behaviour in the presence of defects.
Bayesian Inference for 3D Volumetric Heat Sources Reconstruction from Surfacic IR Imaging
Authors: Groz Marie-Marthe , Abisset-Chavanne Emmanuelle , Meziane Anissa , Sommier Alain , Pradère Christophe
Published: March 2020

The domain of non-destructive testing (NDT) or thermal characterization is currently often done by using contactless methods based on the use of an IR camera to monitor the transient temperature response of a system or sample warmed by using any heat source. Though many techniques use optical excitation (flash lamps, lasers, etc.), some techniques use volumetric sources such as acoustic or induction waves. In this paper, we propose a new inverse processing method, which allows for the estimation of 3D fields of heat sources from surface temperature measurements. This method should be associated with volumetric heat source generation. To validate the method, a volumetric source was generated by the Joule effect in a homogeneous PVC sample using an electrical thin cylindrical wire molded in the material. The inverse processing allows us to retrieve the depth of the wire and its geometrical shape and size. This tool could be a new procedure for retrieving 3D defects on NDT.
First-Principles Study for Gas Sensing of Defective SnSe2 Monolayers
Authors: Cheng Wei-Ying , Fuh Huei-Ru , Chang Ching-Ray
Published: March 2020

We report the interaction between gas molecules (NO2 and NH3) and the SnSe2 monolayers with vacancy and dopants (O and N) for potential applications as gas sensors. Compared with the gas molecular adsorbed on pristine SnSe2 monolayer, the Se-vacancy SnSe2 monolayer obviously enhances sensitivity to NO2 adsorption. The O-doped SnSe2 monolayer shows similar sensitivity to the pristine SnSe2 monolayer when adsorbing NO2 molecule. However, only the N-doped SnSe2 monolayer represents a visible enhancement for NO2 and NH3 adsorption. This work reveals that the selectivity and sensitivity of SnSe2-based gas sensors could be improved by introducing the vacancy or dopants.
A Contemporary Novel Classification of Voltage Stability Indices
Authors: Zaheb Hameedullah , Danish Mir Sayed Shah , Senjyu Tomonobu , Ahmadi Mikaeel , Nazari Abdul Malik , Wali Mohebullah , Khosravy Mahdi , Mandal Paras
Published: March 2020

Within the framework of this study, the inductive analysis of voltage stability indices’ theoretical formulation, functionality, and overall performances are introduced. The prominence is given to investigate and compare the original indices from three main dimensions (formulation, assessment, and application) standpoints, which have been frequently used and recently attracted. The generalizability of an exhaustive investigation on comparison of voltage stability indices seems problematic due to the multiplicity of the indices, and more importantly, their variety in theoretical foundation and performances. This study purports the first-ever framework for voltage stability indices classification for power system analysis. The test results found that indices in the same category are coherent to their theoretical foundation. The paper highlights the fact that each category of the indices is functional for a particular application irrespective of the drawback ranking, and negated the application of the Jacobian matrix-based indices for online application. Finally, the research efforts put forward a novel classification of voltage stability indices within the main three aspects of formulation, assessment, and behavior analysis in a synergistic manner as an exhaustive reference for students, researchers, scholars, and practitioners related to voltage stability analysis. The simulation tools used were MATLAB® and PowerWorld®.
Single-Leg Squat Performance and Reported Pain within Youth Softball Players
Authors: Brittain Abigail R. , Friesen Kenzie B. , Wasserberger Kyle W. , Barfield Jeff W. , Oliver Gretchen D.
Published: March 2020

The purpose of this study was to assess single-leg squat (SLS) performance on reported pain. Forty-two youth softball athletes (13.0 ± 2.0 years; 162.19 ± 9.75 cm; 60.80 ± 14.28 kg) completed a bilateral SLS and a health history questionnaire in which they indicated if they were currently experiencing any pain/discomfort. Due to the clinical significance of the current study, p < 0.10 was classified as nearing significance. A point-biserial correlation was run between the groups (pain and no pain) and all kinematic variables (maximal knee flexion, knee valgus/varus, vertical sacrum displacement, anterior pelvic tilt, and pelvic lateral tilt) at each event (45° descent, maximal knee flexion, and 45° ascent), across each phase (descent, ascent), and between legs. Increased vertical sacrum displacement was correlated with pain at 45° ascent and at maximal knee flexion in the right SLS. Knee valgus at maximal knee flexion, 45° ascent, and in the decent phase of the left SLS was significant. Anterior pelvic tilt in the decent phase of the left SLS and knee valgus and pelvic lateral tilt in the decent phase of the right SLS were found to be significantly correlated with pain. Poor SLS performance was correlated with reported pain.
An Integrated Overview of Ultraviolet Technology for Reversing Titanium Dental Implant Degradation: Mechanism of Reaction and Effectivity
Authors: Razali Masfueh , Ngeow Wei Cheong , Omar Ros Anita , Chai Wen Lin
Published: March 2020

Titanium is widely used as an implanted material in various clinical applications, especially in orthopedics and dental implantology. Following manufacturing and storage, titanium dental implants have the ability to undergo aging, which renders a reduction in osteoblast cellular activity during the healing process, so advancement of a surface treatment to recreate bioactive implant surfaces are required. Ultra-violet (UV) surface treatment has been introduced as a potential solution to reverse the aging process via removal of hydrocarbon contamination on the surface. This narrative review aimed to discuss the current understanding of the mechanism of titanium aging and provide insights into the mechanism that improves the biocompatibility of titanium implants following UV treatment. Additionally, the findings from preclinical and clinical studies is integratively presented. A reference search was performed through the PubMed, Embase, and Scopus databases based on the keywords titanium degradation, titanium aging, photofunctionalization, and UV treatment. Emerging data demonstrated the positive effect of UV light on osteoblast cells with enhanced alkaline phosphatase activity in vitro and increased bone-implant contact in animal studies. Despite limited human studies, the data reported here appear to support the benefit of UV light photofunctionalization on titanium surfaces as an alternative to reverse the titanium aging process. The direction of future research should focus on prospective randomized blinded clinical trials.
Adaptive Real-Time Offloading Decision-Making for Mobile Edges: Deep Reinforcement Learning Framework and Simulation Results
Authors: Park Soohyun , Kwon Dohyun , Kim Joongheon , Lee Youn Kyu , Cho Sungrae
Published: March 2020

This paper proposes a novel dynamic offloading decision method which is inspired by deep reinforcement learning (DRL). In order to realize real-time communications in mobile edge computing systems, an efficient task offloading algorithm is required. When the decision of actions (offloading enabled, i.e., computing in clouds or offloading disabled, i.e., computing in local edges) is made by the proposed DRL-based dynamic algorithm in each unit time, it is required to consider real-time/seamless data transmission and energy-efficiency in mobile edge devices. Therefore, our proposed dynamic offloading decision algorithm is designed for the joint optimization of delay and energy-efficient communications based on DRL framework. According to the performance evaluation via data-intensive simulations, this paper verifies that the proposed dynamic algorithm achieves desired performance.
A Novel Control Strategy to Active Power Filter with Load Voltage Support Considering Current Harmonic Compensation
Authors: Torabi Jafrodi Saeedeh , Ghanbari Mojgan , Mahmoudian Mehrdad , Najafi Arsalan , M. G. Rodrigues Eduardo , Pouresmaeil Edris
Published: March 2020

This paper outlines some modifications to conventional active power filters (APFs) to compensate for the non-linearity of the load current. Since the APFs inject the required non-linearity of the load harmonic current to make the current source sinusoidal, a combination of passive power filters (PPFs) and APFs in series connection are more effective rather than individual usages. The proposed control approach based on sliding mode control (SMC) with a suitable sliding surface selection being applied to the proposed hybrid APF to increase the flexibility and reduce the complexity of the controller. An outstanding tracking process based on the reference current in the rotating dq frame is tested and guarantees the rapid convergence exponentially. An extra control loop is provided for DC link voltage regulation to minimize the DC ripples and control the APF three-phase output voltage levels. The presented solution provides an effective and straightforward load voltage support, maintaining an excellent dynamic performance in load changing and current compensation. The experimental results represent the authenticity of the proposed hybrid APF performance through several different tests, implying a feasible control approach for active filtering systems.
Influence of Vertical Fastener Stiffness on Rail Sound Power Characteristics: Numerical Study and Field Measurement
Authors: Sheng Xi , Zhang Ying , Liu Xiaozhou
Published: March 2020

The aim of this paper is to investigate the influence of vertical fastener stiffness on the sound power characteristics of rail rolling noise. The rail mobility is obtained by using the Timoshenko-beam track model and the spectral element method. The decay rate is obtained by using the periodic track model and the spectral transfer matrix method. Then, the simulation results of the rail mobility and the decay rate are used to calculate the sound power level of the rail subjected to a harmonic point excitation. Furthermore, the influence of vertical fastener stiffness on the rail sound power level is investigated. Finally, field measurements of the rail accelerance and the decay rate are performed to verify the accuracy of models and calculation methods. The results show that the sound power level of the rail subjected to a harmonic point excitation increases with the increase of the frequency and peaks at the center frequency of 800 Hz. When the vertical fastener stiffness decreases from 50 kN/mm, the rail sound power level below the center frequency of 200 Hz gets increased. The increase of the sound power level is most significant at the center frequency which is close to the decreased vertical rail resonance frequency, because in the corresponding one-third octave band the rail mobility amplitude increases significantly while the decay rate decreases considerably. The simulations of the rail accelerance and the decay rate both coincide well with the measurements.
Nonlinear Optimal Control Law of Autonomous Unmanned Surface Vessels
Authors: Chen Yung-Yue , Lee Chun-Yen , Tseng Shao-Han , Hu Wei-Min
Published: March 2020

For energy conservation, nonlinear-optimal-control-law design for marine surface vessels has become a crucial ocean technology for the current ship industry. A well-controlled marine surface vessel with optimal properties must possess accurate tracking capability for accomplishing sailing missions. To achieve this design target, a closed-form nonlinear optimal control law for the trajectory- and waypoint-tracking problem of autonomous marine surface vessels (AUSVs) is presented in this investigation. The proposed approach, based on the optimal control concept, can be effectively applied to generate control commands on marine surface vessels operating in sailing scenarios where ocean environmental disturbances are random and unpredictable. In general, it is difficult to directly obtain a closed-form solution from this optimal tracking problem. Fortunately, by having the adequate choice of state-variable transformation, the nonlinear optimal tracking problem of autonomous marine surface vessels can be converted into a solvable nonlinear time-varying differential equation. The solved closed-form solution can also be acquired with an easy-to-implement control structure for energy-saving purposes.
Automated Vulnerability Detection in Source Code Using Minimum Intermediate Representation Learning
Authors: Li Xin , Wang Lu , Xin Yang , Yang Yixian , Chen Yuling
Published: March 2020

Vulnerability is one of the root causes of network intrusion. An effective way to mitigate security threats is to discover and patch vulnerabilities before an attack. Traditional vulnerability detection methods rely on manual participation and incur a high false positive rate. The intelligent vulnerability detection methods suffer from the problems of long-term dependence, out of vocabulary, coarse detection granularity and lack of vulnerable samples. This paper proposes an automated and intelligent vulnerability detection method in source code based on the minimum intermediate representation learning. First, the sample in the form of source code is transformed into a minimum intermediate representation to exclude the irrelevant items and reduce the length of the dependency. Next, the intermediate representation is transformed into a real value vector through pre-training on an extended corpus, and the structure and semantic information are retained. Then, the vector is fed to three concatenated convolutional neural networks to obtain high-level features of vulnerability. Last, a classifier is trained using the learned features. To validate this vulnerability detection method, an experiment was performed. The empirical results confirmed that compared with the traditional methods and the state-of-the-art intelligent methods, our method has a better performance with fine granularity.
Phylogenetic Distribution, Ultrastructure, and Function of Bacterial Flagellar Sheaths
Authors: Chu Joshua , Liu Jun , Hoover Timothy R.
Published: March 2020

A number of Gram-negative bacteria have a membrane surrounding their flagella, referred to as the flagellar sheath, which is continuous with the outer membrane. The flagellar sheath was initially described in Vibrio metschnikovii in the early 1950s as an extension of the outer cell wall layer that completely surrounded the flagellar filament. Subsequent studies identified other bacteria that possess flagellar sheaths, most of which are restricted to a few genera of the phylum Proteobacteria. Biochemical analysis of the flagellar sheaths from a few bacterial species revealed the presence of lipopolysaccharide, phospholipids, and outer membrane proteins in the sheath. Some proteins localize preferentially to the flagellar sheath, indicating mechanisms exist for protein partitioning to the sheath. Recent cryo-electron tomography studies have yielded high resolution images of the flagellar sheath and other structures closely associated with the sheath, which has generated insights and new hypotheses for how the flagellar sheath is synthesized. Various functions have been proposed for the flagellar sheath, including preventing disassociation of the flagellin subunits in the presence of gastric acid, avoiding activation of the host innate immune response by flagellin, activating the host immune response, adherence to host cells, and protecting the bacterium from bacteriophages.
Distinct Approaches of Raloxifene: Its Far-Reaching Beneficial Effects Implicating the HO-System
Authors: Börzsei Denise , Szabó Renáta , Hoffmann Alexandra , Veszelka Médea , Pávó Imre , Turcsán Zsolt , Viczián Csaba , Kupai Krisztina , Varga Csaba , Pósa Anikó
Published: March 2020

Selective estrogen receptor modulators (SERMs) were discovered in the mid-1900s in connection with estrogen-related pathological conditions. They were developed to antagonize the adverse effects of estrogen and have been shown to be effective against postmenopausal disorders manifested by estrogen deficiency. Raloxifene (RAL), one of the most widely used SERMs, expresses estrogen-like effects on bones, while it is found to be an antagonist on breast and uterus. RAL has multiple beneficial effects throughout the body, including antioxidant and anti-inflammatory properties, because of which it gains particular attention. Additionally, previous studies have revealed that RAL is an efficient modulator of heme-oxygenase (HO) expression. HO, through its general activity, participates in comprehensive cell defense processes, thus the induction of HO by RAL administration indicates a major role in its therapeutic efficacy. In this review, we compile the current knowledge about the overall metabolic, neurocognitive, and cardiovascular effects of RAL involving the cytoprotective HO-system.
Maytenus disticha Extract and an Isolated β-Dihydroagarofuran Induce Mitochondrial Depolarization and Apoptosis in Human Cancer Cells by Increasing Mitochondrial Reactive Oxygen Species
Authors: González-Chavarría Iván , Duprat Felix , Roa Francisco J. , Jara Nery , Toledo Jorge R. , Miranda Felipe , Becerra José , Inostroza Alejandro , Kelling Alexandra , Schilde Uwe , Heydenreich Matthias , Paz Cristian
Published: March 2020

Maytenus disticha (Hook F.), belonging to the Celastraceae family, is an evergreen shrub, native of the central southern mountains of Chile. Previous studies demonstrated that the total extract of M. disticha (MD) has an acetylcholinesterase inhibitory activity along with growth regulatory and insecticidal activities. β-Dihydroagarofurans sesquiterpenes are the most active components in the plant. However, its activity in cancer has not been analyzed yet. Here, we demonstrate that MD has a cytotoxic activity on breast (MCF-7), lung (PC9), and prostate (C4-2B) human cancer cells with an IC50 (µg/mL) of 40, 4.7, and 5 µg/mL, respectively, an increasing Bax/Bcl2 ratio, and inducing a mitochondrial membrane depolarization. The β-dihydroagarofuran-type sesquiterpene (MD-6), dihydromyricetin (MD-9), and dihydromyricetin-3-O-β-glucoside (MD-10) were isolated as the major compounds from MD extracts. From these compounds, only MD-6 showed cytotoxic activity on MCF-7, PC9, and C4-2B with an IC50 of 31.02, 17.58, and 42.19 µM, respectively. Furthermore, the MD-6 increases cell ROS generation, and MD and MD-6 induce a mitochondrial superoxide generation and apoptosis on MCF-7, PC9, and C4-2B, which suggests that the cytotoxic effect of MD is mediated in part by the β-dihydroagarofuran-type that induces apoptosis by a mitochondrial dysfunction.
Salivary Osteocalcin as Potential Diagnostic Marker of Periodontal Bone Destruction among Smokers
Authors: Joseph Betsy , Javali Mukhatar Ahmed , Khader Mohasin Abdul , AlQahtani Saad M. , Mohammed Amanullah
Published: March 2020

The objective of the study was to assess the levels and diagnostic accuracy of salivary osteocalcin (OC), osteonectin (ON), and deoxypyridinoline-containing degradation fragment of the C-terminal telopeptide region of type I collagen (CTX) in adult smokers with periodontal bone destruction. Towards this, ninety systemically healthy patients (groups I: healthy, II: periodontitis with non-smokers, and III: periodontitis with current smokers) were included in the study. The results showed a positive correlation (weak to moderate) was observed for OC, ON, and CTX with probing pocket depth (PPD; r = 0.40, 0.32, and 0.36) and alveolar bone loss (BL; r = 0.58, 0.38, and 0.51) (p < 0.01). Smoker periodontitis was best discriminated from healthy controls using 15.25 ng/mL of OC (AUC: 0.870; 95% CI: 0.757–0.943; YI (Youden Index): 0.693; p < 0.0001). However, with a cut-off of BL at 33.33%, 19.24 ng/mL of salivary OC gave the best discrimination (AUC: 0.809; 95% CI: 0.686–0.900; Se: 80.0%; Sp: 73.47%, and YI: 0.534). A 16.45 ng/mL amount of OC gave excellent discrimination (AUC: 0.811; 95% CI: 0.688–0.901; Se: 92.31%; Sp: 65.22%, and YI: 0.575) among healthy and smoker periodontitis when PD at 6mm was considered as cut-off. Conclusion: The best discrimination between healthy controls and smoker periodontitis was obtained at 15.25 ng/mL of salivary OC.
Mevastatin-Induced AP-1-Dependent HO-1 Expression Suppresses Vascular Cell Adhesion Molecule-1 Expression and Monocyte Adhesion on Human Pulmonary Alveolar Epithelial Cells Challenged with TNF-α
Authors: Yang Chuen-Mao , Lin Chih-Chung , Yang Chien-Chung , Cho Rou-Ling , Hsiao Li-Der
Published: March 2020

Mevastatin (MVS) has been previously shown to induce heme oxygenase (HO)-1 expression through Nox/ROS-dependent PDGFRα/PI3K/Akt/Nrf2/ARE axis in human pulmonary alveolar epithelial cells (HPAEpiCs). However, alternative signaling pathways might involve in MVS-induced HO-1 expression. We found that tumor necrosis factor α (TNFα) induced vascular cell adhesion protein 1 (VCAM-1) expression and NF-κB p65 phosphorylation which were attenuated by pretreatment with MVS via up-regulation of HO-1, determined by Western blot and real-time qPCR. TNFα-induced VCAM-1 expression was attenuated by an NF-κB inhibitor, Bay117082. The inhibitory effects of MVS were reversed by tin protoporphyrin (SnPP)IX (an inhibitor of HO-1 activity). In addition, pretreatment with the inhibitor of pan-Protein kinase C (PKC) (GF109203X), PKCα (Gö6983), Pyk2 (PF431396), p38α MAPK (SB202190), JNK1/2 (SP600125), or AP-1 (Tanshinone IIA), and transfection with their respective siRNAs abolished MVS-induced HO-1 expression in HPAEpiCs. c-Jun (one of AP-1 subunits) was activated by PKCα, Pyk2, p38α MAPK, and JNK1/2, which turned on the transcription of the homx1 gene. The interaction between c-Jun and HO-1 promoter was confirmed by a chromatin immunoprecipitation (ChIP) assay, which was attenuated by these pharmacological inhibitors. These results suggested that MVS induces AP-1/HO-1 expression via PKCα/Pyk2/p38α MAPK- or JNK1/2-dependent c-Jun activation, which further binds with AP-1-binding site on HO-1 promoter and suppresses the TNFα-mediated inflammatory responses in HPAEpiCs. Thus, upregulation of the AP-1/HO-1 system by MVS exerts a potentially therapeutic strategy to protect against pulmonary inflammation.
Oxidative-Antioxidant Imbalance and Impaired Glucose Metabolism in Schizophrenia
Authors: Bryll Amira , Skrzypek Justyna , Krzyściak Wirginia , Szelągowska Maja , Śmierciak Natalia , Kozicz Tamas , Popiela Tadeusz
Published: March 2020

Schizophrenia is a neurodevelopmental disorder featuring chronic, complex neuropsychiatric features. The etiology and pathogenesis of schizophrenia are not fully understood. Oxidative-antioxidant imbalance is a potential determinant of schizophrenia. Oxidative, nitrosative, or sulfuric damage to enzymes of glycolysis and tricarboxylic acid cycle, as well as calcium transport and ATP biosynthesis might cause impaired bioenergetics function in the brain. This could explain the initial symptoms, such as the first psychotic episode and mild cognitive impairment. Another concept of the etiopathogenesis of schizophrenia is associated with impaired glucose metabolism and insulin resistance with the activation of the mTOR mitochondrial pathway, which may contribute to impaired neuronal development. Consequently, cognitive processes requiring ATP are compromised and dysfunctions in synaptic transmission lead to neuronal death, preceding changes in key brain areas. This review summarizes the role and mutual interactions of oxidative damage and impaired glucose metabolism as key factors affecting metabolic complications in schizophrenia. These observations may be a premise for novel potential therapeutic targets that will delay not only the onset of first symptoms but also the progression of schizophrenia and its complications.
Photodynamic Therapy-Based Dendritic Cell Vaccination Suited to Treat Peritoneal Mesothelioma
Authors: Trempolec Natalia , Doix Bastien , Degavre Charline , Brusa Davide , Bouzin Caroline , Riant Olivier , Feron Olivier
Published: March 2020

The potential of dendritic cell (DC)-based immunotherapy to treat cancer is, nowadays, well documented. Still, the clinical success of immune checkpoint inhibitors has dampened the interest in anticancer DC vaccination. For highly life-threatening tumors that are regarded as nonimmunogenic, such as mesothelioma, however, T helper 1 immunity-biased DC-based immunotherapy could still represent an attractive strategy. In this study, we took advantage of photodynamic therapy (PDT) to induce immunogenic cell death to generate mesothelioma cell lysates for DC priming and evaluated such a vaccine to treat peritoneal mesothelioma. We found that the white light in vitro activation of the photosensitizer OR141 led to mesothelioma cell death, together with the release of bona fide danger signals that promote DC maturation. The administration of a PDT-based DC vaccine to mice bearing peritoneal mesothelioma led to highly significant survival when compared with sham or control animals treated with anti-CTLA4 antibodies. This was further supported by a strong CD8+ and CD4+ T cell response, characterized by an increased proliferation, cytotoxic activities and the expression of activation markers, including interferon gamma (IFNγ). Moreover, the PDT-based DC vaccine led to a significant increase in IFNγ+ T cells infiltered within mesothelioma, as determined by flow cytometry and immunohistochemistry. Finally, in vivo tracking of intraperitoneally administered DCs led us to document rapid chemotaxis towards tumor-occupied lymphatics (vs. lipopolysaccharide (LPS)-treated DC). DCs pulsed with PDT-killed mesothelioma cells also exhibited a significant increase in CCR7 receptors, together with an intrinsic capacity to migrate towards the lymph nodes. Altogether, these results indicate that PDT-based DC vaccination is particularly suited to induce a potent immune response against peritoneal mesothelioma.
Correction: McCarthy, C.; et al. Developing Picornaviruses for Cancer Therapy. Cancers 2019, 11, 685
Authors: McCarthy Cormac , Jayawardena Nadishka , Burga Laura N. , Bostina Mihnea
Published: March 2020

The authors wish to make the following corrections to this paper [...]
Management Recommendations for Merkel Cell Carcinoma—A Danish Perspective
Authors: Naseri Simon , Steiniche Torben , Ladekarl Morten , Bønnelykke-Behrndtz Marie Louise , Hölmich Lisbet R. , Langer Seppo W. , Venzo Alessandro , Tabaksblat Elizaveta , Klausen Siri , Skaarup Larsen Mathilde , Junker Niels , Chakera Annette H.
Published: March 2020

Merkel cell carcinoma (MCC) is a rare malignant neuroendocrine carcinoma of the skin with a poor prognosis and an apparent increase in incidence. Due to its rarity, evidence-based guidelines are limited, and there is a lack of awareness among clinicians. This review constitutes the consensus management recommendations developed by the Danish MCC expert group and is based on a systematic literature search. Patients with localized disease are recommended surgical excision and adjuvant radiotherapy to the primary site; however, this may be omitted in patients with MCC with low risk features. Patients with regional lymph node involvement are recommended complete lymph node removal and adjuvant radiotherapy in case of extracapsular disease. Metastatic disease was traditionally treated with chemotherapy, however, recent clinical trials with immune therapy have been promising. Immune checkpoint inhibitors targeting the programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1) axis should therefore be strongly considered as first-line treatment for fit patients. A 5-year follow-up period is recommended involving clinical exam every 3 months for 2 years and every 6 months for the following 3 years and PET-CT one to two times a year or if clinically indicated. These national recommendations are intended to offer uniform patient treatment and hopefully improve prognosis.
Impact of CT-Determined Sarcopenia and Body Composition on Survival Outcome in Patients with Advanced-Stage High-Grade Serous Ovarian Carcinoma
Authors: Kim Se Ik , Kim Taek Min , Lee Maria , Kim Hee Seung , Chung Hyun Hoon , Cho Jeong Yeon , Song Yong Sang
Published: March 2020

This study aimed to investigate the impact of sarcopenia and body composition on survival outcomes in Korean patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). We retrospectively identified patients diagnosed with and treated for International Federation of Gynecology and Obstetrics stage III-IV HGSOC. Skeletal muscle index (SMI) was measured using pre-treatment computed tomography scans at the third lumbar vertebra. Sarcopenia was defined as SMI <39.0 cm2/m2. Patients’ clinicopathologic characteristics and survival outcomes were compared according to sarcopenia presence. For subgroup analysis, we also measured the total fat area from the same image. In total, 76 and 103 patients were assigned to the sarcopenia and control groups, respectively. Comorbidities, stage, serum CA-125 levels, and size of residual tumor after surgery were similar between both groups. After a median follow up of 42.7 months, both groups showed similar progression-free survival (PFS) and overall survival (OS). In subgroup analysis confined to the sarcopenia group, patients with high fat-to-muscle ratio (FMR; ≥2.1, n = 38) showed significantly worse OS than those with low FMR (<2.1, n = 38) (5-year survival rate, 44.7% vs. 80.0%; p = 0.046), whereas PFS was not different (p = 0.365). Multivariate analyses identified high FMR as an independent poor prognostic factor for OS in this group (adjusted hazard ratio, 3.377; 95% confidence interval, 1.170–9.752; p = 0.024). In conclusion, sarcopenia did not influence recurrence rates and survival in Korean patients with advanced-stage HGSOC. However, among the patients with sarcopenia, high FMR was associated with decreased OS.
Pyrolytic Formation of TiO2/Carbon Nanocomposite from Kraft Lignin: Characterization and Photoactivities
Authors: Vadivel Dhanalakshmi , Branciforti Diego Savio , Speltini Andrea , Sturini Michela , Bellani Vittorio , Malaichamy Ilanchelian , Dondi Daniele
Published: March 2020

This article reports on the formation of pyrolytic carbon/TiO2 nanocomposite (p-C/TiO2) by pyrolysis of a mixture of the P25 TiO2 and kraft lignin at 600 °C. The result was characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, UV-visible spectroscopy, electron paramagnetic resonance spectrometry (EPR), thermogravimetry (TGA) and SEM microscopy. Its photocatalytic activity was ascertained using three classes of chemical probes, namely (i) degradation of methylene blue (MB) and rhodamine-B (RhB) dyes in UV light-irradiated aqueous suspensions, (ii) depletion of phenol and (iii) degradation of antibiotics. The p-C/TiO2 nanocomposite is a strong phisisorbent of both MB and RhB nearly twofold with respect to neat TiO2. Although it is nearly twofold more photoactive toward the degradation of MB (0.091 min−1 versus 0.047 min−1), it is not with regard to RhB degradation (0.064 min−1 versus 0.060 min−1). For the degradation of phenol in aqueous media (pH 3), pristine TiO2 was far more effective than p-C/TiO2 for oxygenated suspensions (17.6 × 10−3 mM min−1 versus 4.3 × 10−3 mM min−1). Under an argon atmosphere, the kinetics were otherwise identical. The activity of the material was tested also for a real application in the degradation of a fluoroquinolone antibiotic such as enrofloxacin (ENR) in tap water. It is evident that the photoactivity of a semiconductor photocatalyst is not a constant, but it does depend on the nature of the substrate used and on the experimental conditions. It is also argued that the use of dyes to assess photocatalytic activities when suspensions are subjected to visible light irradiation is to be discouraged as the dyes act as electron transfer photosensitizers and or can undergo photodegradation from their excited states.
In Vitro Generation of Oocyte Like Cells and Their In Vivo Efficacy: How Far We have been Succeeded
Authors: Bharti Dinesh , Jang Si-Jung , Lee Sang-Yun , Lee Sung-Lim , Rho Gyu-Jin
Published: March 2020

In the last few decades, stem cell therapy has grown as a boon for many pathological complications including female reproductive disorders. In this review, a brief description of available strategies that are related to stem cell-based in vitro oocyte-like cell (OLC) development are given. We have tried to cover all the aspects and latest updates of the in vitro OLC developmental methodologies, marker profiling, available disease models, and in vivo efficacies, with a special focus on mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs) usage. The differentiation abilities of both the ovarian and non-ovarian stem cell sources under various induction conditions have shown different effects on morphological alterations, proliferation- and size-associated developments, hormonal secretions under gonadotropic stimulations, and their neo-oogenesis or folliculogenesis abilities after in vivo transplantations. The attainment of characters like oocyte-like morphology, size expansion, and meiosis initiation have been found to be major obstacles during in vitro oogenesis. A number of reports have either lacked in vivo studies or have shown their functional incapability to produce viable and healthy offspring. Though researchers have gained many valuable insights regarding in vitro gametogenesis, still there are many things to do to make stem cell-derived OLCs fully functional.
Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer
Authors: Law Andrew M. K. , Valdes-Mora Fatima , Gallego-Ortega David
Published: March 2020

The emergence of immunotherapy has been an astounding breakthrough in cancer treatments. In particular, immune checkpoint inhibitors, targeting PD-1 and CTLA-4, have shown remarkable therapeutic outcomes. However, response rates from immunotherapy have been reported to be varied, with some having pronounced success and others with minimal to no clinical benefit. An important aspect associated with this discrepancy in patient response is the immune-suppressive effects elicited by the tumour microenvironment (TME). Immune suppression plays a pivotal role in regulating cancer progression, metastasis, and reducing immunotherapy success. Most notably, myeloid-derived suppressor cells (MDSC), a heterogeneous population of immature myeloid cells, have potent mechanisms to inhibit T-cell and NK-cell activity to promote tumour growth, development of the pre-metastatic niche, and contribute to resistance to immunotherapy. Accumulating research indicates that MDSC can be a therapeutic target to alleviate their pro-tumourigenic functions and immunosuppressive activities to bolster the efficacy of checkpoint inhibitors. In this review, we provide an overview of the general immunotherapeutic approaches and discuss the characterisation, expansion, and activities of MDSCs with the current treatments used to target them either as a single therapeutic target or synergistically in combination with immunotherapy.
Carbohydrate and Amino Acid Metabolism as Hallmarks for Innate Immune Cell Activation and Function
Authors: Zhao Haoxin , Raines Lydia N. , Huang Stanley Ching-Cheng
Published: March 2020

Immune activation is now understood to be fundamentally linked to intrinsic and/or extrinsic metabolic processes which are essential for immune cells to survive, proliferate, and perform their effector functions. Moreover, disruption or dysregulation of these pathways can result in detrimental outcomes and underly a number of pathologies in both communicable and non-communicable diseases. In this review, we discuss how the metabolism of carbohydrates and amino acids in particular can modulate innate immunity and how perturbations in these pathways can result in failure of these immune cells to properly function or induce unfavorable phenotypes.
Exosomes are the Driving Force in Preparing the Soil for the Metastatic Seeds: Lessons from the Prostate Cancer
Authors: Saber Saber H. , Ali Hamdy E. A. , Gaballa Rofaida , Gaballah Mohamed , Ali Hamed I. , Zerfaoui Mourad , Abd Elmageed Zakaria Y.
Published: March 2020

Exosomes are nano-membrane vesicles that various cell types secrete during physiological and pathophysiological conditions. By shuttling bioactive molecules such as nucleic acids, proteins, and lipids to target cells, exosomes serve as key regulators for multiple cellular processes, including cancer metastasis. Recently, microvesicles have emerged as a challenge in the treatment of prostate cancer (PCa), encountered either when the number of vesicles increases or when the vesicles move into circulation, potentially with an ability to induce drug resistance, angiogenesis, and metastasis. Notably, the exosomal cargo can induce the desmoplastic response of PCa-associated cells in a tumor microenvironment (TME) to promote PCa metastasis. However, the crosstalk between PCa-derived exosomes and the TME remains only partially understood. In this review, we provide new insights into the metabolic and molecular signatures of PCa-associated exosomes in reprogramming the TME, and the subsequent promotion of aggressive phenotypes of PCa cells. Elucidating the molecular mechanisms of TME reprogramming by exosomes draws more practical and universal conclusions for the development of new therapeutic interventions when considering TME in the treatment of PCa patients.
Urine-Derived Stem Cells: Applications in Regenerative and Predictive Medicine
Authors: Bento Guida , Shafigullina Aygul K. , Rizvanov Albert A. , Sardão Vilma A. , Macedo Maria Paula , Oliveira Paulo J.
Published: March 2020

Despite being a biological waste, human urine contains a small population of cells with self-renewal capacity and differentiation potential into several cell types. Being derived from the convoluted tubules of nephron, renal pelvis, ureters, bladder and urethra, urine-derived stem cells (UDSC) have a similar phenotype to mesenchymal stroma cells (MSC) and can be reprogrammed into iPSC (induced pluripotent stem cells). Having simple, safer, low-cost and noninvasive collection procedures, the interest in UDSC has been growing in the last decade. With great potential in regenerative medicine applications, UDSC can also be used as biological models for pharmacology and toxicology tests. This review describes UDSC biological characteristics and differentiation potential and their possible use, including the potential of UDSC-derived iPSC to be used in drug discovery and toxicology, as well as in regenerative medicine. Being a new cellular platform amenable to noninvasive collection for disease stratification and personalized therapy could be a future application for UDSC.
An Overview of Crucial Dietary Substances and Their Modes of Action for Prevention of Neurodegenerative Diseases
Authors: Pogačnik Lea , Ota Ajda , Poklar Ulrih Nataša
Published: March 2020

Neurodegenerative diseases, namely Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis are becoming one of the main health concerns due to the increasing aging of the world’s population. These diseases often share the same biological mechanisms, including neuroinflammation, oxidative stress, and/or protein fibrillation. Recently, there have been many studies published pointing out the possibilities to reduce and postpone the clinical manifestation of these deadly diseases through lifelong consumption of some crucial dietary substances, among which phytochemicals (e.g., polyphenols) and endogenous substances (e.g., acetyl-L-carnitine, coenzyme Q10, n-3 poysaturated fatty acids) showed the most promising results. Another important issue that has been pointed out recently is the availability of these substances to the central nervous system, where they have to be present in high enough concentrations in order to exhibit their neuroprotective properties. As so, such the aim of this review is to summarize the recent findings regarding neuroprotective substances, their mechanisms of action, as well as to point out therapeutic considerations, including their bioavailability and safety for humans.