bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary Patterns and Associated Factors Among Adolescents in Malaysia: Findings from Adolescent Nutrition Survey 2017
Authors: Man Cheong Siew , Salleh Ruhaya , Ahmad Mohamad Hasnan , Baharudin Azli , Koon Poh Bee , Aris Tahir
Published: May 2020

Balanced diet in the early stages of life plays a role in optimum growth and maintains good health status of adolescents. Dietary habits that are established during adolescence will sustain till adulthood. Therefore, this present study aims to identify the dietary patterns and to determine factors associated with dietary patterns in terms of socio-demographic characteristics, locality of schools, ethnicity, eating habits, self-perceived weight status, and food label reading habit among adolescents in Malaysia. Data from the Adolescent Nutrition Survey (ANS) 2017 was used for the present study. ANS is a population representative school-based cross-sectional study among school-going adolescents from primary four to secondary five from schools in 13 states and three federal territories registered under the Ministry of Education Malaysia. A self-administrated questionnaire was used to collect information on socio-demographic characteristics, locality of schools, ethnicity, eating habits, self-perceived weight status, and food label reading habit. A pre-tested face-to-face food frequency questionnaire (FFQ) was used to collect information on food group intake frequency. Dietary patterns were identified by using exploratory factor analysis and associated factors, using complex sample general linear model (GLM) analysis. All statistical analyses were carried out at 95% confidence interval or p-value < 0.05. The dietary patterns identified are healthy, unhealthy, and alternative proteins. The healthy dietary pattern was significantly associated with the types of school and ethnicity. The unhealthy dietary pattern was significantly associated with the locality of schools, ethnicity, frequency of snacks intake per week, frequency of eating out per week, self-perceived weight status, and food label reading habit. Significant associations were found between alternative proteins dietary pattern and locality of schools, ethnicity, and types of school. This study found that there is a disparity of dietary patterns between different ethnicity, locality of schools, and types of school. We recommend strategies of specifying ethnicity and geographical area to improve dietary patterns of adolescents in Malaysia.
Physiological and Psychological Effects of Watching Videos of Different Durations Showing Urban Bamboo Forests with Varied Structures
Authors: Wang Yuqian , Jiang Mingyan , Huang Yinshu , Sheng Zhiyi , Huang Xiao , Lin Wei , Chen Qibing , Li Xi , Luo Zhenghua , Lv Bingyang
Published: May 2020

This study illustrated the physiological and psychological effects of watching videos of different durations showing bamboo forests with varied structures. Physiological indicators, including EEG (electroencephalogram), blood pressure, skin conductance, and pulse, were monitored in 180 Chinese university students (mean age: 20.72 ± 2.56 years) while they were watching bamboo videos. Before and after watching the videos, their psychological indicators, including positive and negative moods, were measured using the Profile of Mood States questionnaire. After watching the bamboo videos of different durations, all of the physiological indicators responded to the stimulation after only 1 min. The indicators showed different trends at 1, 3 and 5 min. EEG decreased and then was maintained at a stable level after 1 min, and the high β, low β, and α waves had no significant differences between 1, 3 and 5 min. Blood pressure dropped to a stable state after 3 min, and the decline was significantly different greater after 3 min than after 1 min. Skin conductance increased for 1 to 5 min, and it did not stabilize after a long time (5 min). Pulse decreased after 1 min but increased after 5 min. After watching the videos with bamboo of varying structures, the physiological and psychological indicators showed significantly different changes. Skin conductance significantly increased (mean value: 6.78%), and the amount of sweat was more effectively reduced, thereby reducing tension, when the students viewed videos of sympodial bamboo forests compared with monopodial bamboo forests. Bamboo forests with a higher canopy density (0.83–0.85) could significantly decrease α waves (mean value: 1.50 Hz), relaxing the human body. High β and low β waves showed greater decreases, with tension reduced more effectively, when bamboo forests with a low tilt ratio (< 1.5%) were viewed. Bamboo forests with neat undergrowth could have more beneficial physiological and psychological effects on the human body.
Psychophysiological Responses in Emergency Medical Technician Students during Simulated Work Activities in a Hot Environment
Authors: Gerhart Hayden D. , Fiorentini Amy B. , Storti Kristi L. , Alman Robert , Bayles Madeline P. , Pesci Louis , Seo Yongsuk
Published: May 2020

This study compared physiological responses and cognitive performance during simulated work activities in heat to a thermoneutral condition. First responders perform physically demanding activities in a hot environment which may impose additional burdens on tactical personnel during daily tasks. Ten healthy (8 men and 2 women) participants performed two consecutive simulated work activities with two repetitions of each activity (10 min walking on treadmill and 15 sandbag lifts) under heat and thermoneutral conditions. A Stroop color word test (SCWT) and total mood disturbance (TMD) were obtained at first and second baseline (B1, B2), after a 30-min resting period (B3), and recovery (R1). At the end of the trial, core temperature (Tc), skin temperature (tsk), and mean body temperature (Tb) were higher in the heat condition compared to neutral condition (all p ≤ 0.05), whereas oxygen uptake, heart rate, and mean arterial pressure were not significantly different between conditions. There were no differences in scores of SCWT and TMD between conditions. However, TMD was significantly improved after two successive bouts of exercise compared to B3 (all p ≤ 0.05). This investigation shows that two successive simulated work activities did not induce the detrimental influence on thermoregulatory and cognitive responses. Extended work activities in a hot and humid environment may impose a psychophysiological burden and need to be investigated.
Concentration Variability of Water-Soluble Ions during the Acceptable and Exceeded Pollution in an Industrial Region
Authors: Švédová Barbora , Raclavská Helena , Kucbel Marek , Růžičková Jana , Raclavský Konstantin , Koliba Miroslav , Juchelková Dagmar
Published: May 2020

This study investigates the chemical composition of water-soluble inorganic ions at eight localities situated in the Moravian–Silesian Region (the Czech Republic) at the border with Poland. Water-soluble inorganic ions were monitored in the winter period of 2018 (January, 11 days and February, 5 days). The set was divided into two periods: the acceptable period (the 24-h concentration of PM10 < 50 µg/m3) and the period with exceeded pollution (PM10 ˃ 50 µg/m3). Air quality in the Moravian–Silesian Region and Upper Silesia is among the most polluted in Europe, especially in the winter season when the concentration of PM10 is repeatedly exceeded. The information on the occurrence and behaviour of water-soluble inorganic ions in the air during the smog episodes in Europe is insufficient. The concentrations of water-soluble ions (chlorides, sulphates, nitrates, ammonium ions, potassium) during the exceeded period are higher by two to three times compared with the acceptable period. The major anions for both acceptable period and exceeded pollution are nitrates. During the period of exceeded pollution, percentages of water-soluble ions in PM10 decrease while percentages of carbonaceous matter and insoluble particles (fly ash) increase.
How Are Wearable Activity Trackers Adopted in Older Adults? Comparison between Subjective Adoption Attitudes and Physical Activity Performance
Authors: Lee Byung Cheol , Xie Junfei , Ajisafe Toyin , Kim Sung-Hee
Published: May 2020

Wearable activity trackers can motivate older adults to engage in the recommended daily amount of physical activity (PA). However, individuals may not maintain their use of the trackers over a longer period. To investigate the attitudes of activity tracker adoption and their effects on actual PA performance, we conducted a three-month study. We gave activity trackers to 16 older adults and assessed attitudes on activity tracker adoption through a survey during the study period. We extracted participants’ PA measures, step counts, and moderate and vigorous physical activity (MVPA) times. We observed significant differences in adoption attitudes during the three different periods (χ2(2, 48) = 6.27, p < 0.05), and PA measures followed similar decreasing patterns (F(83, 1357) = 12.56, 13.94, p < 0.00001). However, the Pearson correlation analysis (r = 0.268, p = 0.284) and a Bland–Altman plot indicated a bias between two PA measures. Positive attitudes at the initial stage did not persist through the study period, and both step counts and length of MVPA time showed waning patterns in the study period. The longitudinal results from both measures demonstrated the patterns of old adults’ long-term use and adoption. Considering the accuracy of the activity tracker and older adults’ athletic ability, MVPA times are more likely to be a reliable measure of older adults’ long-term use and successful adoption of activity trackers than step counts. The results support the development of better activity tracker design guidelines that would facilitate long-term adoption among older adults.
Analysis of a Sports-Educational Program in Prisons
Authors: Ortega Vila Gema , Abad Robles Manuel Tomás , Robles Rodríguez José , Durán González Luis Javier , Franco Martín Jorge , Jiménez Sánchez Ana Concepción , Giménez Fuentes-Guerra Francisco Javier
Published: May 2020

The aim of this study was to analyze the implementation of a sports-educational program in prisons where the Real Madrid Foundation’s Social-Sports Program is carried out. For that purpose, a survey of 468 inmates was conducted at 21 prisons in Spain where the Real Madrid Foundation implements its program (441 men (94.23%) and 27 women (5.77%)). Inmates stated that the program had had a favorable influence on their life in prison and considered that their participation in the program might have a significant influence on the likelihood of them continuing to play sports when they are released. In addition, inmates felt that they had learned a great deal about the contents relating to football and the values they had worked on, and that the program had had a very positive effect on their overall development as a person.
Improving the Size Homogeneity of Multicore Superparamagnetic Iron Oxide Nanoparticles
Authors: Yeh Barry J. , Anani Tareq , David Allan E.
Published: May 2020

Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely explored for use in many biomedical applications. Methods for synthesis of magnetic nanoparticle (MNP), however, typically yield multicore structures with broad size distribution, resulting in suboptimal and variable performance in vivo. In this study, a new method for sorting SPIONs by size, labeled diffusive magnetic fractionation (DMF), is introduced as an improvement over conventional magnetic field flow fractionation (MFFF). Unlike MFFF, which uses a constant magnetic field to capture particles, DMF utilizes a pulsed magnetic field approach that exploits size-dependent differences in the diffusivity and magnetic attractive force of SPIONs to yield more homogenous particle size distributions. To compare both methods, multicore SPIONs with a broad size distribution (polydispersity index (PdI) = 0.24 ± 0.05) were fractionated into nine different-sized SPION subpopulations, and the PdI values were compared. DMF provided significantly improved size separation compared to MFFF, with eight out of the nine fractionations having significantly lower PdI values (p value < 0.01). Additionally, the DMF method showed a high particle recovery (>95%), excellent reproducibility, and the potential for scale-up. Mathematical models were developed to enable optimization, and experimental results confirmed model predictions (R2 = 0.98).
microRNAs as Promising Biomarkers of Platelet Activity in Antiplatelet Therapy Monitoring
Authors: Krammer Teresa L. , Mayr Manuel , Hackl Matthias
Published: May 2020

Given the high morbidity and mortality of cardiovascular diseases (CVDs), novel biomarkers for platelet reactivity are urgently needed. Ischemic events in CVDs are causally linked to platelets, small anucleate cells important for hemostasis. The major side-effect of antiplatelet therapy are life-threatening bleeding events. Current platelet function tests are not sufficient in guiding treatment decisions. Platelets host a broad spectrum of microRNAs (miRNAs) and are a major source of cell-free miRNAs in the blood stream. Platelet-related miRNAs have been suggested as biomarkers of platelet activation and assessment of antiplatelet therapy responsiveness. Platelets release miRNAs upon activation, possibly leading to alterations of plasma miRNA levels in conjunction with CVD or inadequate platelet inhibition. Unlike current platelet function tests, which measure platelet activation ex vivo, signatures of platelet-related miRNAs potentially enable the assessment of in vivo platelet reactivity. Evidence suggests that some miRNAs are responsive to platelet inhibition, making them promising biomarker candidates. In this review, we explain the secretion of miRNAs upon platelet activation and discuss the potential use of platelet-related miRNAs as biomarkers for CVD and antiplatelet therapy monitoring, but also highlight remaining gaps in our knowledge and uncertainties regarding clinical utility. We also elaborate on technical issues and limitations concerning plasma miRNA quantification.
The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds
Authors: Legler Juliette , Zalko Daniel , Jourdan Fabien , Jacobs Miriam , Fromenty Bernard , Balaguer Patrick , Bourguet William , Munic Kos Vesna , Nadal Angel , Beausoleil Claire , Cristobal Susana , Remy Sylvie , Ermler Sibylle , Margiotta-Casaluci Luigi , Griffin Julian L. , Blumberg Bruce , Chesné Christophe , Hoffmann Sebastian , Andersson Patrik L. , Kamstra Jorke H.
Published: May 2020

The purpose of this project report is to introduce the European “GOLIATH” project, a new research project which addresses one of the most urgent regulatory needs in the testing of endocrine-disrupting chemicals (EDCs), namely the lack of methods for testing EDCs that disrupt metabolism and metabolic functions. These chemicals collectively referred to as “metabolism disrupting compounds” (MDCs) are natural and anthropogenic chemicals that can promote metabolic changes that can ultimately result in obesity, diabetes, and/or fatty liver in humans. This project report introduces the main approaches of the project and provides a focused review of the evidence of metabolic disruption for selected EDCs. GOLIATH will generate the world’s first integrated approach to testing and assessment (IATA) specifically tailored to MDCs. GOLIATH will focus on the main cellular targets of metabolic disruption—hepatocytes, pancreatic endocrine cells, myocytes and adipocytes—and using an adverse outcome pathway (AOP) framework will provide key information on MDC-related mode of action by incorporating multi-omic analyses and translating results from in silico, in vitro, and in vivo models and assays to adverse metabolic health outcomes in humans at real-life exposures. Given the importance of international acceptance of the developed test methods for regulatory use, GOLIATH will link with ongoing initiatives of the Organisation for Economic Development (OECD) for test method (pre-)validation, IATA, and AOP development.
Tunneling Nanotubes-Mediated Protection of Mesenchymal Stem Cells: An Update from Preclinical Studies
Authors: Soundara Rajan Thangavelu , Gugliandolo Agnese , Bramanti Placido , Mazzon Emanuela
Published: May 2020

Tunneling nanotubes (TNTs) are thin membrane elongations among the cells that mediate the trafficking of subcellular organelles, biomolecules, and cues. Mesenchymal stem cells (MSCs) receive substantial attention in tissue engineering and regenerative medicine. Many MSCs-based clinical trials are ongoing for dreadful diseases including cancer and neurodegenerative diseases. Mitochondrial trafficking through TNTs is one of the mechanisms used by MSCs to repair tissue damage and to promote tissue regeneration. Preclinical studies linked with ischemia, oxidative stress, mitochondrial damage, inflammation, and respiratory illness have demonstrated the therapeutic efficacy of MSCs via TNTs-mediated transfer of mitochondria and other molecules into the injured cells. On the other hand, MSCs-based cancer studies showed that TNTs may modulate chemoresistance in tumor cells as a result of mitochondrial trafficking. In the present review, we discuss the role of TNTs from preclinical studies associated with MSCs treatment. We discuss the impact of TNTs formation between MSCs and cancer cells and emphasize to study the importance of TNTs-mediated MSCs protection in disease models.
A Novel 3D Bioprinter Using Direct-Volumetric Drop-On-Demand Technology for Fabricating Micro-Tissues and Drug-Delivery
Authors: Grottkau Brian E. , Hui Zhixin , Pang Yonggang
Published: May 2020

Drop-on-demand (DOD) 3D bioprinting technologies currently hold the greatest promise for generating functional tissues for clinical use and for drug development. However, existing DOD 3D bioprinting technologies have three main limitations: (1) droplet volume inconsistency; (2) the ability to print only bioinks with low cell concentrations and low viscosity; and (3) problems with cell viability when dispensed under high pressure. We report our success developing a novel direct-volumetric DOD (DVDOD) 3D bioprinting technology that overcomes each of these limitations. DVDOD can produce droplets of bioink from <10 nL in volume using a direct-volumetric mechanism with <± 5% volumetric percent accuracy in an accurate spatially controlled manner. DVDOD has the capability of dispensing bioinks with high concentrations of cells and/or high viscosity biomaterials in either low- or high-throughput modes. The cells are subjected to a low pressure during the bioprinting process for a very short period of time that does not negatively impact cell viability. We demonstrated the functions of the bioprinter in two distinct manners: (1) by using a high-throughput drug-delivery model; and (2) by bioprinting micro-tissues using a variety of different cell types, including functional micro-tissues of bone, cancer, and induced pluripotent stem cells. Our DVDOD technology demonstrates a promising platform for generating many types of tissues and drug-delivery models.
Concentration and Duration of Indoxyl Sulfate Exposure Affects Osteoclastogenesis by Regulating NFATc1 via Aryl Hydrocarbon Receptor
Authors: Liu Wen-Chih , Shyu Jia-Fwu , Lim Paik Seong , Fang Te-Chao , Lu Chien-Lin , Zheng Cai-Mei , Hou Yi-Chou , Wu Chia-Chao , Lin Yuh-Feng , Lu Kuo-Cheng
Published: May 2020

Indoxyl sulfate (IS) is a chronic kidney disease (CKD)-specific renal osteodystrophy metabolite that affects the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a transcription factor promoting osteoclastogenesis. However, the mechanisms underlying the regulation of NFATc1 by IS remain unknown. It is intriguing that the Aryl hydrocarbon receptor (AhR) plays a key role in osteoclastogenesis, since IS is an endogenous AhR agonist. This study investigates the relationship between IS concentration and osteoclast differentiation in Raw 264.7 cells, and examines the effects of different IS concentrations on NFATc1 expression through AhR signaling. Our data suggest that both osteoclastogenesis and NFATc1 are affected by IS through AhR signaling in both dose- and time-dependent manners. Osteoclast differentiation increases with short-term, low-dose IS exposure and decreases with long-term, high-dose IS exposure. Different IS levels switch the role of AhR from that of a ligand-activated transcription factor to that of an E3 ubiquitin ligase. We found that the AhR nuclear translocator may play an important role in the regulation of these dual functions of AhR under IS treatment. Altogether, this study demonstrates that the IS/AhR/NFATc1 signaling axis plays a critical role in osteoclastogenesis, indicating a potential role of AhR in the pathology and abnormality of bone turnover in CKD patients.
Methylmercury Poisoning Induces Cardiac Electrical Remodeling and Increases Arrhythmia Susceptibility and Mortality
Authors: Santos Ruybal Mara Cristina P. , Gallego Monica , Sottani Thais Bazoti B. , Medei Emiliano H. , Casis Oscar , Nascimento Jose Hamilton M.
Published: May 2020

This study aims to investigate the cardiac electrical remodeling associated with intoxication by methylmercury (MeHg). We evaluated the chronic effects of MeHg on in vivo electrocardiograms and on ex vivo action potentials and depolarizing (ICa-L) and repolarizing (Ito) currents. The acute effect of MeHg was evaluated on HEK293 cells expressing human ERG, Kv4.3 and KCNQ1/KCNE1 channels. Chronic MeHg treatment increased QTc and Tpeak–Tend interval duration, prolonged action potential duration and decreased amplitude of Ito and ICa-L. In addition, heterologously expressed IhKv4.3, IhERG or IhKCNQ1/KCNE1 decreased after acute exposure to MeHg at subnanomolar range. The introduction of the in vitro effects of MeHg in a computer model of human ventricular action potentials triggered early afterdepolarizations and arrhythmia. In conclusion, cardiac electrical remodeling induced by MeHg poisoning is related to the reduction of Ito and ICa-L. The acute effect of MeHg on hKv4.3; hERG and hKCNQ1/KCNE1 currents and their transposition to in silico models show an association between MeHg intoxication and acquired Long QT Syndrome in humans. MeHg can exert its high toxicity either after chronic or acute exposure to concentrations as low as picomolar.
Clustering of the ζ-Chain Can Initiate T Cell Receptor Signaling
Authors: Ma Yuanqing , Lim Yean J. , Benda Aleš , Lou Jieqiong , Goyette Jesse , Gaus Katharina
Published: May 2020

T cell activation is initiated when ligand binding to the T cell receptor (TCR) triggers intracellular phosphorylation of the TCR-CD3 complex. However, it remains unknown how biophysical properties of TCR engagement result in biochemical phosphorylation events. Here, we constructed an optogenetic tool that induces spatial clustering of ζ-chain in a light controlled manner. We showed that spatial clustering of the ζ-chain intracellular tail alone was sufficient to initialize T cell triggering including phosphorylation of ζ-chain, Zap70, PLCγ, ERK and initiated Ca2+ flux. In reconstituted COS-7 cells, only Lck expression was required to initiate ζ-chain phosphorylation upon ζ-chain clustering, which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed ζ-chain clusters at the plasma membrane. Taken together, our data demonstrated the biophysical relevance of receptor clustering in TCR signaling.
Serotonin in Health and Disease
Authors: De Deurwaerdère Philippe , Di Giovanni Giuseppe
Published: May 2020

The International Journal of Molecular Sciences Special Issue “Serotonin in health and diseases” covers several aspects of the multiple and still mysterious functions of serotonin (5-hydroxytryptamine; 5-HT). 5-HT is neurotransmitter acting in the central nervous system (CNS), blood factor, and neurohormone controlling the function of several peripheral organs. Beyond its widespread implication in physiology, the 5-HT system is involved in numerous diseases of the CNS (e.g., depression, anxiety, schizophrenia, obsessive-compulsive disorders, addiction, Parkinson’s disease) and peripheral organs (e.g., gastrointestinal disorders, cardiac arrhythmia, hypertension). The Special Issue includes 14 articles dealing with molecular and cellular effects of 5-HT in periphery and CNS, from functional aspects in lower animals to clinical practices. Beyond physiology, the Special Issue also covers the influence of 5-HT and its receptors in the mechanism of action of psychoactive molecules including antipsychotics, antidepressants, and drug of abuse. The recent progress made on the function and dysfunction of the 5-HT system will certainly increase the understanding of the widespread role of 5-HT ultimately leading to better apprehend its targeting in human diseases.
Does the Urothelium of Old Mice Regenerate after Chitosan Injury as Quickly as the Urothelium of Young Mice?
Authors: Erzar Eva , Kerec Kos Mojca , Lakota Katja , Veranič Peter , Erman Andreja
Published: May 2020

The aging of organisms leads to a decreased ability of tissue to regenerate after injury. The regeneration of the bladder urothelium after induced desquamation with biopolymer chitosan has been studied in young mice but not in old mice. Chitosan is a suitable inducer of urothelial desquamation because it is known to be non-toxic. We used chitosan for desquamation of urothelial cells in order to compare the dynamics of urothelial regeneration after injury between young and old mice. Our aim was to determine whether the urothelial function and structure of old mice is restored as fast as in young mice, and to evaluate the inflammatory response due to chitosan treatment. We discovered that the urothelial function restored comparably fast in both age groups and that the urothelium of young and old mice recovered within 5 days after injury, although the onset of proliferation and differentiation appeared later in old mice. Acute inflammation markers showed some differences in the inflammatory response in young versus old mice, but in both age groups, chitosan caused short-term acute inflammation. In conclusion, the restoration of urothelial function is not impaired in old mice, but the regeneration of the urothelial structure in old mice slightly lags behind the regeneration in young mice.
Targeting Mitochondria during Cold Storage to Maintain Proteasome Function and Improve Renal Outcome after Transplantation
Authors: Lo Sorena B. , Blaszak Richard T. , Parajuli Nirmala
Published: May 2020

Kidney transplantation is the preferred treatment for end-stage kidney disease (ESKD). Compared to maintenance dialysis, kidney transplantation results in improved patient survival and quality of life. Kidneys from living donors perform best; however, many patients with ESKD depend on kidneys from deceased donors. After procurement, donor kidneys are placed in a cold-storage solution until a suitable recipient is located. Sadly, prolonged cold storage times are associated with inferior transplant outcomes; therefore, in most situations when considering donor kidneys, long cold-storage times are avoided. The identification of novel mechanisms of cold-storage-related renal damage will lead to the development of new therapeutic strategies for preserving donor kidneys; to date, these mechanisms remain poorly understood. In this review, we discuss the importance of mitochondrial and proteasome function, protein homeostasis, and renal recovery during stress from cold storage plus transplantation. Additionally, we discuss novel targets for therapeutic intervention to improve renal outcomes.
Myostatin Inhibits Vascular Smooth Muscle Cell Proliferation and Local 14q32 microRNA Expression, But Not Systemic Inflammation or Restenosis
Authors: Goossens Eveline A.C. , de Vries Margreet R. , Jukema J. Wouter , Quax Paul H.A. , Nossent A. Yaël
Published: May 2020

Myostatin is a negative regulator of muscle cell growth and proliferation. Furthermore, myostatin directly affects the expression of 14q32 microRNAs by binding the 14q32 locus. Direct inhibition of 14q32 microRNA miR-495-3p decreased postinterventional restenosis via inhibition of both vascular smooth muscle cell (VSMC) proliferation and local inflammation. Here, we aimed to investigate the effects of myostatin in a mouse model for postinterventional restenosis. In VSMCs in vitro, myostatin led to the dose-specific downregulation of 14q32 microRNAs miR-433-3p, miR-494-3p, and miR-495-3p. VSMC proliferation was inhibited, where cell migration and viability remained unaffected. In a murine postinterventional restenosis model, myostatin infusion did not decrease restenosis, neointimal area, or lumen stenosis. Myostatin inhibited expression of both proliferation marker PCNA and of 14q32 microRNAs miR-433-3p, miR-494-3p, and miR-495-3p dose-specifically in cuffed femoral arteries. However, 14q32 microRNA expression remained unaffected in macrophages and macrophage activation as well as macrophage influx into lesions were not decreased. In conclusion, myostatin did not affect postinterventional restenosis. Although myostatin inhibits 14q32 microRNA expression and proliferation in VSMCs, myostatin had no effect on macrophage activation and infiltration. Our findings underline that restenosis is driven by both VSMC proliferation and local inflammation. Targeting only one of these components is insufficient to prevent restenosis.
Ultramicronized Palmitoylethanolamide and Paracetamol, a New Association to Relieve Hyperalgesia and Pain in a Sciatic Nerve Injury Model in Rat
Authors: Peritore Alessio Filippo , Siracusa Rosalba , Fusco Roberta , Gugliandolo Enrico , D’Amico Ramona , Cordaro Marika , Crupi Rosalia , Genovese Tiziana , Impellizzeri Daniela , Cuzzocrea Salvatore , Di Paola Rosanna
Published: May 2020

Inflammation is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration; moreover, damage to peripheral nerves can cause a loss of sensory function and produces persistent neuropathic pain. To date, various potential approaches for neuropathic pain have focused on controlling neuroinflammation. The aim of this study was to investigate the neuroprotective effects of a new association of ultramicronized Palmitoylethanolamide (PEAum), an Autacoid Local Injury Antagonist Amide (ALIAmide) with analgesic and anti-inflammatory properties, with Paracetamol, a common analgesic, in a rat model of sciatic nerve injury (SNI). The association of PEAum–Paracetamol, in a low dose (5 mg/kg + 30 mg/kg), was given by oral gavage daily for 14 days after SNI. PEAum–Paracetamol association was able to reduce hyperalgesia, mast cell activation, c-Fos and nerve growth factor (NGF) expression, neural histological damage, cytokine release, and apoptosis. Furthermore, the analgesic action of PEAum–Paracetamol could act in a synergistic manner through the inhibition of the NF-κB pathway, which leads to a decrease of cyclooxygenase 2-dependent prostaglandin E2 (COX-2/PGE2) release. In conclusion, we demonstrated that PEAum associated with Paracetamol was able to relieve pain and neuroinflammation after SNI in a synergistic manner, and this therapeutic approach could be relevant to decrease the demand of analgesic drugs.
Identification, Localization in the Central Nervous System and Novel Myostimulatory Effect of Allatostatins in Tenebrio molitor Beetle
Authors: Lubawy Jan , Marciniak Paweł , Rosiński Grzegorz
Published: May 2020

Allatostatins (ASTs) are pleiotropic insect neuropeptides that are potent myoinhibitors of muscle contractions. In this study, we identified and immunolocalized peptides from the MIP/AST and PISCF/AST families in the nervous system of a model beetle, Tenebrio molitor. Neurons containing MIPs were immunolocalized in the brains of adults and the ventral nerve cords of larvae, pupae and imagines of this species as well as in the retrocerebral complex. PISCFs were immunolocalized in the ventral nerve cord of all stages as well as the brain of the adult beetle. Faint signals were also observed in the corpus allatum but not in the corpus cardiacum. The results allowed us to deduce the sequences of three neuropeptides belonging to MIP/ASTs, Tenmo-MIP4—NWGQFGXWa, Tenmo-MIP5—SKWDNFRGSWa and Tenmo-MIP6—EPAWSNLKGIWa, and one peptide from the PISCF/AST family, QSRYXQCYFNPISCX. Furthermore, we showed for the first time myostimulatory action of endogenous MIP/ASTs. Tenmo-MIP5 caused dose-dependent stimulation of the contractile activity of the beetle oviduct muscles, showing a sigmoidal curve up to 81.20% at the 10−8 M concentration, and the EC50 value for the myostimulatory effect of this peptide was 8.50 × 10−12 M. This is the first report of myostimulatory action of an endogenous myoinhibitory peptide in insect muscles.
Novel 3′-Substituted-1′,2′,4′-Oxadiazole Derivatives of 18βH-Glycyrrhetinic Acid and Their O-Acylated Amidoximes: Synthesis and Evaluation of Antitumor and Anti-Inflammatory Potential In Vitro and In Vivo
Authors: Markov Andrey V. , Sen’kova Aleksandra V. , Popadyuk Irina I. , Salomatina Oksana V. , Logashenko Evgeniya B. , Komarova Nina I. , Ilyina Anna A. , Salakhutdinov Nariman F. , Zenkova Marina A.
Published: May 2020

A series of novel 18βH-glycyrrhetinic acid (GA) derivatives containing 3′-(alkyl/phenyl/pyridin(-2″, -3″, and -4″)-yl)-1′,2′,4′-oxadiazole moieties at the C-30 position were synthesized by condensation of triterpenoid’s carboxyl group with corresponding amidoximes and further cyclization. Screening of the cytotoxicity of novel GA derivatives on a panel of tumor cell lines showed that the 3-acetoxy triterpenoid intermediates—O-acylated amidoxime 3a-h—display better solubility under bioassay conditions and more pronounced cytotoxicity compared to their 1′,2′,4′-oxadiazole analogs 4f-h (median IC50 = 7.0 and 49.7 µM, respectively). Subsequent replacement of the 3-acetoxy group by the hydroxyl group of pyridin(-2″, 3″, and -4″)-yl-1′,2′,4′-oxadiazole-bearing GA derivatives produced compounds 5f-h, showing the most pronounced selective toxicity toward tumor cells (median selectivity index (SI) > 12.1). Further detailed analysis of the antitumor activity of hit derivative 5f revealed its marked proapoptotic activity and inhibitory effects on clonogenicity and motility of HeLa cervical carcinoma cells in vitro, and the metastatic growth of B16 melanoma in vivo. Additionally, the comprehensive in silico study revealed intermediate 3d, bearing the tert-butyl moiety in O-acylated amidoxime, as a potent anti-inflammatory candidate, which was able to effectively inhibit inflammatory response induced by IFNγ in macrophages in vitro and carrageenan in murine models in vivo, probably by primary interactions with active sites of MMP9, neutrophil elastase, and thrombin. Taken together, our findings provide a basis for a better understanding of the structure–activity relationship of 1′,2′,4′-oxadiazole-containing triterpenoids and reveal two hit molecules with pronounced antitumor (5f) and anti-inflammatory (3d) activities.
Keratin Biomembranes as a Model for Studying Onychomycosis
Authors: Valkov Anton , Zinigrad Michael , Sobolev Alexander , Nisnevitch Marina
Published: May 2020

Difficulties in obtaining human nails that are large enough for examining the penetration of drug formulations led us to produce keratin films regenerated from human hair. We assume that these films can simulate human nail plates in drug penetration and permeation tests and can serve as a biological model for studying onychomycosis. The films were formed from keratin extracted from human hair using dithiothreitol, urea and thiourea. The obtained keratin extract was dispensed into Teflon rings and dried at 40 °C and then cured at 110 °C. The structure, surface morphology, chemical characterization and thermal stability of the films were characterized and were compared to those of human nail, hair and bovine hoof samples using SDS-electrophoresis, scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). The structure of the obtained films was found to be closer to human nails than to hair or bovine hooves. The keratin films were infected with Trichophyton rubrum and were proven to be appropriate for serving as a model for studying onychomycosis.
Peritoneal Fluid Cytokines Reveal New Insights of Endometriosis Subphenotypes
Authors: Zhou Jieliang , Chern Bernard Su Min , Barton-Smith Peter , Phoon Jessie Wai Leng , Tan Tse Yeun , Viardot-Foucault Veronique , Ku Chee Wai , Tan Heng Hao , Chan Jerry Kok Yen , Lee Yie Hou
Published: May 2020

Endometriosis is a common inflammatory gynecological disorder which causes pelvic scarring, pain, and infertility, characterized by the implantation of endometrial-like lesions outside the uterus. The peritoneum, ovaries, and deep soft tissues are the commonly involved sites, and endometriotic lesions can be classified into three subphenotypes: superficial peritoneal endometriosis (PE), ovarian endometrioma (OE), and deep infiltrating endometriosis (DIE). In 132 women diagnosed laparoscopically with and without endometriosis (n = 73, 59 respectively), and stratified into PE, OE, and DIE, peritoneal fluids (PF) were characterized for 48 cytokines by using multiplex immunoassays. Partial-least-squares-regression analysis revealed distinct subphenotype cytokine signatures—a six-cytokine signature distinguishing PE from OE, a seven-cytokine signature distinguishing OE from DIE, and a six-cytokine-signature distinguishing PE from DIE—each associated with different patterns of biological processes, signaling events, and immunology. These signatures describe endometriosis better than disease stages (p < 0.0001). Pathway analysis revealed the association of ERK1 and 2, AKT, MAPK, and STAT4 linked to angiogenesis, cell proliferation, migration, and inflammation in the subphenotypes. These data shed new insights on the pathophysiology of endometriosis subphenotypes, with the potential to exploit the cytokine signatures to stratify endometriosis patients for targeted therapies and biomarker discovery.
The Effects of High Molecular Weight Hyaluronic Acid Eye Drop Application in Environmental Dry Eye Stress Model Mice
Authors: Kojima Takashi , Nagata Taeko , Kudo Haruka , Müller-Lierheim Wolfgang G. K. , van Setten Gysbert-Botho , Dogru Murat , Tsubota Kazuo
Published: May 2020

Hyaluronic acid (HA) ophthalmic solution is widely used in dry eye treatment worldwide. However, there are no reports comparing the dry eye treatment effects of high molecular weight HA with low molecular weight HA. Sixty eight-week-old C57BL/6 mice were assigned to the following 6 groups and exposed to environmental dry eye stress (EDES) that mimics office work environment: (1) 0.1% low molecular weight HA (LMWHA) eye drops, (2) 0.3% LMWHA eye drops, (3) 3% diquafosol sodium (DQ) eye drops, (4) 0.15% high molecular weight HA (HMWHA) eye drops, (5) no treatment with exposure to EDES (EDES+/Treatment−), and (6) no treatment without exposure to EDES (EDES−/Treatment−). After EDES, the HMWHA group had significantly longer break-up time (BUT) than the 0.1%, 0.3% LMWHA groups and the DQ group. After EDES, the HMWHA group had significantly lower lissamine green staining scores than the LMWHA and DQ groups. Subepithelial presumed dendritic cell density in the HMWHA group was significantly lower than the EDES+/Treatment− group. After EDES exposure, Conjunctival Muc5AC mRNA expression in the HMWHA group was significantly higher than the 0.1 and 0.3% LMWHA groups. Ophthalmic HMWHA solution may have a better dry eye treatment effect than LMWHA or DQ solution, owing to its anti-inflammatory effect.
AMPK and the Need to Breathe and Feed: What’s the Matter with Oxygen?
Authors: Evans A. Mark , Hardie D. Grahame
Published: May 2020

We live and to do so we must breathe and eat, so are we a combination of what we eat and breathe? Here, we will consider this question, and the role in this respect of the AMP-activated protein kinase (AMPK). Emerging evidence suggests that AMPK facilitates central and peripheral reflexes that coordinate breathing and oxygen supply, and contributes to the central regulation of feeding and food choice. We propose, therefore, that oxygen supply to the body is aligned with not only the quantity we eat, but also nutrient-based diet selection, and that the cell-specific expression pattern of AMPK subunit isoforms is critical to appropriate system alignment in this respect. Currently available information on how oxygen supply may be aligned with feeding and food choice, or vice versa, through our motivation to breathe and select particular nutrients is sparse, fragmented and lacks any integrated understanding. By addressing this, we aim to provide the foundations for a clinical perspective that reveals untapped potential, by highlighting how aberrant cell-specific changes in the expression of AMPK subunit isoforms could give rise, in part, to known associations between metabolic disease, such as obesity and type 2 diabetes, sleep-disordered breathing, pulmonary hypertension and acute respiratory distress syndrome.
An Insight into the Role of Trissolcus mitsukurii as Biological Control Agent of Halyomorpha halys in Northeastern Italy
Authors: Scaccini Davide , Falagiarda Martina , Tortorici Francesco , Martinez-Sañudo Isabel , Tirello Paola , Reyes-Domínguez Yazmid , Gallmetzer Andreas , Tavella Luciana , Zandigiacomo Pietro , Duso Carlo , Pozzebon Alberto
Published: May 2020

Sustainable strategies such as classical or augmentative biological control are currently being evaluated for the long-term management of the alien invasive pest Halyomorpha halys (Stål) (Hemiptera: Pentatomidae). A three-year study carried out in northeastern Italy was performed to investigate the distribution and field performance of the H. halys egg parasitoid Trissolcus mitsukurii (Ashmead) (Hymenoptera: Scelionidae), in comparison with other parasitoid species. In the study area, adventive populations of T. mitsukurii were present since 2016, representing the earliest detection of this species in Europe. Trissolcus mitsukurii was the most abundant parasitoid and showed a higher “parasitoid impact” (i.e., number of parasitized eggs over the total number of field-collected eggs) compared to the other species, i.e., Anastatus bifasciatus (Geoffroy) (Hymenoptera: Eupelmidae), Trissolcus basalis (Wollaston) and Trissolcus kozlovi Rjachovskij (Hymenoptera: Scelionidae). The hyperparasitoid Acroclisoides sinicus (Huang and Liao) (Hymenoptera: Pteromalidae) was also recorded. Phylogenetic analysis of T. mitsukurii population distinguished two clades, one covering samples from Italy, Japan and China, the other from South Korea. The present study provides promising results for the biological control of a pest that is having a dramatic impact on a wide range of crops worldwide.
Climate Change May Restrict the Predation Efficiency of Mesocyclops aspericornis (Copepoda: Cyclopidae) on Aedes aegypti (Diptera: Culicidae) Larvae
Authors: Tuno Nobuko , Phong Tran Vu , Takagi Masahiro
Published: May 2020

(1) Dengue is the most spread mosquito-borne viral disease in the world, and vector control is the only available means to suppress its prevalence, since no effective treatment or vaccine has been developed. A biological control program using copepods that feed on mosquito larvae has been practiced in Vietnam and some other countries, but the application of copepods was not always successful. (2) To understand why the utility of copepods varies, we evaluated the predation efficiency of a copepod species (Mesocyclops aspericornis) on a vector species (Aedes aegypti) by laboratory experiments under different temperatures, nutrition and prey-density conditions. (3) We found that copepod predation reduced intraspecific competition among Aedes larvae and then shortened the survivor’s aquatic life and increased their pupal weight. In addition, the predatory efficiency of copepods was reduced at high temperatures. Furthermore, performance of copepod offspring fell when the density of mosquito larvae was high, probably because mosquito larvae had adverse effects on copepod growth through competition for food resources. (4) These results suggest that the increase in mosquitoes will not be suppressed solely by the application of copepods if the density of mosquito larvae is high or ambient temperature is high. We need to consider additional control methods in order to maintain the efficiency of copepods to suppress mosquito increase.
Biochemical Mechanisms, Cross-resistance and Stability of Resistance to Metaflumizone in Plutella xylostella
Authors: Shen Jun , Li Zhao , Li Dongyang , Wang Rumeng , Zhang Shuzhen , You Hong , Li Jianhong
Published: May 2020

The diamondback moth, Plutella xylostella (L.) is an important pest of cruciferous crops worldwide. It has developed resistance to many conventional and novel insecticide classes. Metaflumizone belongs to the new chemical class of semicarbazone insecticides. To delay the development of metaflumizone resistance in P. xylostella and to guide insecticide use in the field, the biochemical mechanisms, cross-resistance spectrum, and stability of resistance to metaflumizone were studied in a laboratory-selected resistant strain (metaflu-SEL). Synergism tests with the carboxylesterase inhibitor triphenyl phosphate (TPP), the glutathione S-transferase depletor diethyl maleate (DEM), and the P450 inhibitor piperonyl butoxide(PBO) had no obvious effect on metaflumizone in the metaflu-SEL strain and the susceptible strain (SS) of P. xylostella, with synergism ratios that ranged from 1.02 to 1.86. Biochemical studies revealed that the cytochrome P450-dependent monooxygenase increased only 1.13-fold in the metaflu-SEL strain compared with the UNSEL stain; meanwhile, carboxylesterase and glutathione S-transferase activity showed no difference. These results suggest that these detoxification enzymes may be not actively involved in metaflumizone resistance. Furthermore, the metaflu-SEL population showed a moderate level of cross-resistance to indoxacarb (11.63-fold), but only very low cross-resistance to spinosad (1.75-fold), spinetoram (3.52-fold), abamectin (2.81-fold), beta-cypermethrin (0.71-fold), diafenthiuron (0.79-fold), chlorantraniliprole (2.16-fold), BT (WG-001) (3.34-fold), chlorfenapyr (0.49-fold), and chlorfluazuron (0.97-fold). Moreover, metaflumizone resistance decreased from 1087.85- to 1.23-fold in the metaflu-SEL strain after 12 generations without exposure to metaflumizone. These results are useful for formulating insecticide resistance management strategies to control P. xylostella and to delay the development of metaflumizone resistance in the field.
CNN-Based Page Segmentation and Object Classification for Counting Population in Ottoman Archival Documentation
Authors: Can Yekta Said , Kabadayı M. Erdem
Published: May 2020

Historical document analysis systems gain importance with the increasing efforts in the digitalization of archives. Page segmentation and layout analysis are crucial steps for such systems. Errors in these steps will affect the outcome of handwritten text recognition and Optical Character Recognition (OCR) methods, which increase the importance of the page segmentation and layout analysis. Degradation of documents, digitization errors, and varying layout styles are the issues that complicate the segmentation of historical documents. The properties of Arabic scripts such as connected letters, ligatures, diacritics, and different writing styles make it even more challenging to process Arabic script historical documents. In this study, we developed an automatic system for counting registered individuals and assigning them to populated places by using a CNN-based architecture. To evaluate the performance of our system, we created a labeled dataset of registers obtained from the first wave of population registers of the Ottoman Empire held between the 1840s and 1860s. We achieved promising results for classifying different types of objects and counting the individuals and assigning them to populated places.