bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Listening to Music on Wingate Anaerobic Test Performance. A Systematic Review and Meta-Analysis
Authors: Castañeda-Babarro Arkaitz , Marqués-Jiménez Diego , Calleja-González Julio , Viribay Aitor , León-Guereño Patxi , Mielgo-Ayuso Juan
Published: June 2020

Background: There are many athletes who like to listen to music while making a high intensity effort. However, research into the effects of listening to music on athletic performance has provided controversial results, and it is suggested that the timing and type of music might affect the anaerobic performance response. Purpose: The main aim of the current systematic review and meta-analysis was to analyze the effects while listening to music tasks via the 30 s Wingate anaerobic test (WAnT) on absolute performance and relative peak power (APP and RPP), absolute and relative mean power (AMP and RMP), and fatigue index (FI). Methods: PRISMA guidelines were used as a basis for conducting this systematic review, with inclusion criteria being set out according to the PICOS model. Computer-based literature research was undertaken until 10 March 2020 using the following online databases: PubMed/Medline, WOS, Cochrane Library, and Scopus. The literature was reviewed with regard to the effects of listening to music on the WAnT using several music variables on: APP, RPP, AMP, RMP and FI. Hedges’ g formula was used to calculate both standard mean differences and 95% confidence intervals, in order to establish continuous outcomes. Furthermore, the I2 statistic evaluated systematic differences (heterogeneity) together with a random effect meta-analysis model. Results: This systematic review included nine articles that researched into the effects of music on WAnT performance (six studies describe improvements in APP and/or RPP, four in AMP and/or RMP and three in FI). The random effects model was used to undertake a final meta-analysis, with standardized mean differences (SMD) and magnitude of standardized mean differences (MSMD) (Hedges’ g) being pooled accordingly. The resulting meta-analysis incorporated eight studies that had been previously published, with results showing that there were no apparent beneficial effects on APP (p = 0.09), AMP (p = 0.33) and FI (p = 0.46) as a consequence of listening to music. However, listening to music showed beneficial effects on RPP (SMD: 0.65; 95%: CI 0.35 to 0.96; MSMD: moderate; I2, 0%; p < 0.001) and RMP (SMD: 1.03; 95%: CI, 0.63 to 1.42; MSMD: trivial; I2, 0%; p < 0.001). Conclusion: This systematic review and meta-analysis has shown that listening to music during the WAnT might physiologically enhance relative anaerobic exercise performance, although reasons remain speculative.
The State of Vaccine Confidence in Poland: A 2019 Nationwide Cross-Sectional Survey
Authors: Furman Filip M. , Zgliczyński Wojciech Stefan , Jankowski Mateusz , Baran Tomasz , Szumowski Łukasz , Pinkas Jarosław
Published: June 2020

Vaccination is considered as one of the most successful and cost-effective public health interventions. This study aimed to assess (1) the attitudes and behaviors towards mandatory childhood vaccination, with particular emphasis on socio-economic factors determining the vaccine confidence among adults in Poland as well as to (2) identify the potential impact of anti-vaccination movement on vaccination coverage among children and adolescents aged ≤19 years. This cross-sectional study was carried in 2019 on a nationwide, representative sample of 1079 individuals aged 18 and over in Poland (53.7% females). Most of the respondents (74.6%) agreed or strongly agreed that mandatory vaccinations are safe, and only 8% of participants neglected the safety of vaccines. The results of multivariate analysis showed that the lowest level of vaccine confidence was observed among participants aged 25–34 years (aOR: 0.48, 95%CI: 0.29–0.80; p = 0.01). There was a positive correlation (r = 0.35; p < 0.001) between trust in doctors and vaccine confidence. Moreover, there was a positive correlation between trust in scientific knowledge and vaccine confidence (r = 0.19; p < 0.001). Also, a negative correlation (r = −0.13; p < 0.001) between trust in horoscopes and vaccine confidence was observed. Most of the parents declared (97.7%), that their children were vaccinated following the national immunization programme. However, 8.5% of parents who currently vaccinated their children declared that they would stop vaccinating children when vaccination obligation will be abolished. This study demonstrates relatively high confidence in mandatory vaccination among adults in Poland. While most of society trusts in vaccine safety, young adults are the least trustful of vaccinations.
Fear of Missing Out, Mental Wellbeing, and Social Connectedness: A Seven-Day Social Media Abstinence Trial
Authors: Brown Lorna , Kuss Daria J.
Published: June 2020

Smartphones aid the constant accessibility of social media (SM) applications, and these devices and platforms have become a key part of our everyday lives and needs. Previous research has focused on the psychological impact of social media use (SMU) and SM abstinence has only received limited attention. Therefore, employing a combination of an experimental within-subjects mixed methodology using surveys to obtain both quantitative and qualitative data, this study aimed to compare psychosocial factors of fear of missing out (FoMO), mental wellbeing (MWB), and social connectedness (SC) before and after seven days of SM abstinence. Results revealed that participants (N = 61) experienced a significant increase in MWB and SC, and a significant decrease in FoMO and smartphone use following SM abstinence. There was a significant positive relationship between MWB and SC change scores and a significant negative relationship between SC and FoMO change scores. There were no significant differences in levels of SMU before abstinence or across genders in FoMO, MWB, and SC change scores. Thematic analysis revealed coping, habit, and boredom as motivations for SMU, and notification distractions presenting a challenge for successful abstinence from SM. Participants indicated that abstinence resulted in the perceived need to fill their time with non-SM applications. Finally, thematic analysis revealed mixed experiences of perceived connectivity in the absence of SMU. Findings present implications for the importance of unplugging from SM for temporary periods because scrolling through SM to fill time is a key motivator of SMU, and notifications encourage SMU and trigger FoMO.
Connectivity as a Mediating Mechanism in the Cybervictimization Process
Authors: Cuadrado-Gordillo Isabel , Fernández-Antelo Inmaculada
Published: June 2020

This paper explores the relationship between social connectivity and cybervictimization as it is mediated by psychosocial variables such as social identity and self-esteem. Likewise, it analyses the moderating role in that relationship played by adolescents’ perception of cyberbullying. The sample consisted of 2072 adolescents (48.7% girls) aged between 14 and 18 (Mean = 15.78, Standard Deviation = 1.02) years. Through the use of five questionnaires, an explanatory model is constructed that shows the direct and indirect relationships between the factors analysed, the predictive values that social connectivity can reach when applied to the virtual environment, and the perception of cyberbullying in the victimization processes. The results indicate that self-esteem and social identity are protective factors in the establishment of healthy virtual relationships and avoidance of cybervictimization situations. Moreover, the equation of cyberbullying with aggressive or maladaptive styles of humour has an indirect influence on the link between connectivity and cybervictimization.
Phloem Exudate Protein Profiles during Drought and Recovery Reveal Abiotic Stress Responses in Tomato Vasculature
Authors: Ogden Aaron J. , Bhatt Jishnu J. , Brewer Heather M. , Kintigh Jack , Kariuki Samwel M. , Rudrabhatla Sairam , Adkins Joshua N. , Curtis Wayne R.
Published: June 2020

Drought is the leading cause of agricultural yield loss among all abiotic stresses, and the link between water deficit and phloem protein contents is relatively unexplored. Here we collected phloem exudates from Solanum lycopersicum leaves during periods of drought stress and recovery. Our analysis identified 2558 proteins, the most abundant of which were previously localized to the phloem. Independent of drought, enrichment analysis of the total phloem exudate protein profiles from all samples suggests that the protein content of phloem sap is complex, and includes proteins that function in chaperone systems, branched-chain amino acid synthesis, trehalose metabolism, and RNA silencing. We observed 169 proteins whose abundance changed significantly within the phloem sap, either during drought or recovery. Proteins that became significantly more abundant during drought include members of lipid metabolism, chaperone-mediated protein folding, carboxylic acid metabolism, abscisic acid signaling, cytokinin biosynthesis, and amino acid metabolism. Conversely, proteins involved in lipid signaling, sphingolipid metabolism, cell wall organization, carbohydrate metabolism, and a mitogen-activated protein kinase are decreased during drought. Our experiment has achieved an in-depth profiling of phloem sap protein contents during drought stress and recovery that supports previous findings and provides new evidence that multiple biological processes are involved in drought adaptation.
Revisiting NO2 as Protecting Group of Arginine in Solid-Phase Peptide Synthesis
Authors: Alhassan Mahama , Kumar Ashish , Lopez John , Albericio Fernando , de la Torre Beatriz G.
Published: June 2020

The protection of side-chain arginine in solid-phase peptide synthesis requires attention since current protecting groups have several drawbacks. Herein, the NO2 group, which is scarcely used, has been revisited. This work shows that it prevents the formation of δ-lactam, the most severe side-reaction during the incorporation of Arg. Moreover, it is stable in solution for long periods and can be removed in an easy-to-understand manner. Thus, this protecting group can be removed while the protected peptide is still anchored to the resin, with SnCl2 as reducing agent in mild acid conditions using 2-MeTHF as solvent at 55 °C. Furthermore, we demonstrate that sonochemistry can facilitate the removal of NO2 from multiple Arg-containing peptides.
SpeS: A Novel Superantigen and Its Potential as a Vaccine Adjuvant against Strangles
Authors: Dominguez-Medina C. Coral , Rash Nicola L. , Robillard Sylvain , Robinson Carl , Efstratiou Androulla , Broughton Karen , Parkhill Julian , Holden Matthew T.G. , Lopez-Alvarez Maria R. , Paillot Romain , Waller Andrew S.
Published: June 2020

Bacterial superantigens (sAgs) are powerful activators of the immune response that trigger unspecific T cell responses accompanied by the release of proinflammatory cytokines. Streptococcus equi (S. equi) and Streptococcus zooepidemicus (S. zooepidemicus) produce sAgs that play an important role in their ability to cause disease. Strangles, caused by S. equi, is one of the most common infectious diseases of horses worldwide. Here, we report the identification of a new sAg of S. zooepidemicus, SpeS, and show that mutation of the putative T cell receptor (TCR)-binding motif (YAY to IAY) abrogated TCR-binding, whilst maintaining interaction with major histocompatibility complex (MHC) class II molecules. The fusion of SpeS and SpeSY39I to six S. equi surface proteins using two different peptide linkers was conducted to determine if MHC class II-binding properties were maintained. Proliferation assays, qPCR and flow cytometry analysis showed that SpeSY39I and its fusion proteins induced less mitogenic activity and interferon gamma expression when compared to SpeS, whilst retaining Antigen-Presenting Cell (APC)-binding properties. Our data suggest that SpeSY39I-surface protein fusions could be used to direct vaccine antigens towards antigen-presenting cells in vivo with the potential to enhance antigen presentation and improve immune responses.
Bcr-Abl Tyrosine Kinase Inhibitors in the Treatment of Pediatric CML
Authors: Carofiglio Francesca , Lopalco Antonio , Lopedota Angela , Cutrignelli Annalisa , Nicolotti Orazio , Denora Nunzio , Stefanachi Angela , Leonetti Francesco
Published: June 2020

The therapeutic approach to Chronic Myeloid Leukemia (CML) has changed since the advent of the tyrosine kinase inhibitor (TKI) imatinib, which was then followed by the second generation TKIs dasatinib, nilotinib, and, finally, by ponatinib, a third-generation drug. At present, these therapeutic options represent the first-line treatment for adults. Based on clinical experience, imatinb, dasatinib, and nilotinib have been approved for children even though the studies that were concerned with efficacy and safety toward pediatric patients are still awaiting more specific and high-quality data. In this scenario, it is of utmost importance to prospectively validate data extrapolated from adult studies to set a standard therapeutic management for pediatric CML by employing appropriate formulations on the basis of pediatric clinical trials, which allow a careful monitoring of TKI-induced adverse effects especially in growing children exposed to long-term therapy.
Differences between Well-Differentiated Neuroendocrine Tumors and Ductal Adenocarcinomas of the Pancreas Assessed by Multi-Omics Profiling
Authors: Starzyńska Teresa , Karczmarski Jakub , Paziewska Agnieszka , Kulecka Maria , Kuśnierz Katarzyna , Żeber-Lubecka Natalia , Ambrożkiewicz Filip , Mikula Michał , Kos-Kudła Beata , Ostrowski Jerzy
Published: June 2020

Most pancreatic neuroendocrine tumors (PNETs) are indolent, while pancreatic ductal adenocarcinomas (PDACs) are particularly aggressive. To elucidate the basis for this difference and to establish the biomarkers, by using the deep sequencing, we analyzed somatic variants across coding regions of 409 cancer genes and measured mRNA/miRNA expression in nine PNETs, eight PDACs, and four intestinal neuroendocrine tumors (INETs). There were 153 unique somatic variants considered pathogenic or likely pathogenic, found in 50, 57, and 24 genes in PDACs, PNETs, and INETs, respectively. Ten and 11 genes contained a pathogenic mutation in at least one sample of all tumor types and in PDACs and PNETs, respectively, while 28, 34, and 11 genes were found to be mutated exclusively in PDACs, PNETs, and INETs, respectively. The mRNA and miRNA transcriptomes of PDACs and NETs were distinct: from 54 to 1659 differentially expressed mRNAs and from 117 to 250 differentially expressed miRNAs exhibited high discrimination ability and resulted in models with an area under the receiver operating characteristics curve (AUC-ROC) >0.9 for both miRNA and mRNA. Given the miRNAs high stability, we proposed exploring that class of RNA as new pancreatic tumor biomarkers.
MAP/ERK Signaling in Developing Cognitive and Emotional Function and Its Effect on Pathological and Neurodegenerative Processes
Authors: Albert-Gascó Héctor , Ros-Bernal Francisco , Castillo-Gómez Esther , Olucha-Bordonau Francisco E.
Published: June 2020

The signaling pathway of the microtubule-associated protein kinase or extracellular regulated kinase (MAPK/ERK) is a common mechanism of extracellular information transduction from extracellular stimuli to the intracellular space. The transduction of information leads to changes in the ongoing metabolic pathways and the modification of gene expression patterns. In the central nervous system, ERK is expressed ubiquitously, both temporally and spatially. As for the temporal ubiquity, this signaling system participates in three key moments: (i) Embryonic development; (ii) the early postnatal period; and iii) adulthood. During embryonic development, the system is partly responsible for the patterning of segmentation in the encephalic vesicle through the FGF8-ERK pathway. In addition, during this period, ERK directs neurogenesis migration and the final fate of neural progenitors. During the early postnatal period, ERK participates in the maturation process of dendritic trees and synaptogenesis. During adulthood, ERK participates in social and emotional behavior and memory processes, including long-term potentiation. Alterations in mechanisms related to ERK are associated with different pathological outcomes. Genetic alterations in any component of the ERK pathway result in pathologies associated with neural crest derivatives and mental dysfunctions associated with autism spectrum disorders. The MAP-ERK pathway is a key element of the neuroinflammatory pathway triggered by glial cells during the development of neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis, as well as prionic diseases. The process triggered by MAPK/ERK activation depends on the stage of development (mature or senescence), the type of cellular element in which the pathway is activated, and the anatomic neural structure. However, extensive gaps exist with regards to the targets of the phosphorylated ERK in many of these processes.
Capsaicin-Sensitive Sensory Nerves and the TRPV1 Ion Channel in Cardiac Physiology and Pathologies
Authors: Szabados Tamara , Gömöri Kamilla , Pálvölgyi Laura , Görbe Anikó , Baczkó István , Helyes Zsuzsanna , Jancsó Gábor , Ferdinandy Péter , Bencsik Péter
Published: June 2020

Cardiovascular diseases, including coronary artery disease, ischemic heart diseases such as acute myocardial infarction and postischemic heart failure, heart failure of other etiologies, and cardiac arrhythmias, belong to the leading causes of death. Activation of capsaicin-sensitive sensory nerves by the transient receptor potential vanilloid 1 (TRPV1) capsaicin receptor and other receptors, as well as neuropeptide mediators released from them upon stimulation, play important physiological regulatory roles. Capsaicin-sensitive sensory nerves also contribute to the development and progression of some cardiac diseases, as well as to mechanisms of endogenous stress adaptation leading to cardioprotection. In this review, we summarize the role of capsaicin-sensitive afferents and the TRPV1 ion channel in physiological and pathophysiological functions of the heart based mainly on experimental results and show their diagnostic or therapeutic potentials. Although the actions of several other channels or receptors expressed on cardiac sensory afferents and the effects of TRPV1 channel activation on different non-neural cell types in the heart are not precisely known, most data suggest that stimulation of the TRPV1-expressing sensory nerves or stimulation/overexpression of TRPV1 channels have beneficial effects in cardiac diseases.
Inactivation of APC Induces CD34 Upregulation to Promote Epithelial-Mesenchymal Transition and Cancer Stem Cell Traits in Pancreatic Cancer
Authors: Hsieh Mei Jen , Chiu Tai-Jan , Lin Yu Chun , Weng Ching-Chieh , Weng Yu-Ting , Hsiao Chang-Chun , Cheng Kuang-hung
Published: June 2020

Pancreatic cancer (PC) is a highly lethal malignancy due to the cancer routinely being diagnosed late and having a limited response to chemotherapy. Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic malignant tumor, representing more than 85% of all pancreatic cancers. In the present study, we characterized the phenotypes of concomitant P53 and APC mutations in pancreatic neoplasms driven by the oncogene KRAS in genetically modified mice (GEMM). In this GEMM setting, APC haploinsufficiency coupled with P53 deletion and KRASG12D activation resulted in an earlier appearance of pancreatic intraepithelial neoplasia (PanIN) lesions and progressed rapidly to highly invasive and metastatic PDAC. Through a microarray analysis of murine PDAC cells derived from our APC-deficient PDAC model, we observed that APC loss leads to upregulated CD34 expression in PDAC. CD34 is a member of a family of single-pass transmembrane proteins and is selectively expressed in hematopoietic progenitor cells, vascular endothelial cells, interstitial precursor cells, and various interstitial tumor cells. However, the functional roles of CD34 in pancreatic cancer remain unclear. Thus, in this study, we explored the mechanisms regarding how CD34 promotes the deterioration of pancreatic malignancy. Our results demonstrated that the increased expression of CD34 induced by APC inactivation promotes the invasion and migration of PDAC cells, which may relate to PDAC metastasis in vivo. Collectively, our study provides first-line evidence to delineate the association between CD34 and the APC/Wnt pathway in PDAC, and reveals the potential roles of CD34 in PDAC progression.
Norditerpenoids with Selective Anti-Cholinesterase Activity from the Roots of Perovskia atriplicifolia Benth.
Authors: Ślusarczyk Sylwester , Senol Deniz F. Sezer , Abel Renata , Pecio Łukasz , Pérez-Sánchez Horacio , Cerón-Carrasco José P. , den-Haan Helena , Banerjee Priyanka , Preissner Robert , Krzyżak Edward , Oleszek Wiesław , E. Orhan Ilkay , Matkowski Adam
Published: June 2020

Inhibition of cholinesterases remains one of a few available treatment strategies for neurodegenerative dementias such as Alzheimer’s disease and related conditions. The current study was inspired by previous data on anticholinesterase properties of diterpenoids from Perovskia atriplicifolia and other Lamiaceae species. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition by the three new natural compounds—(1R,15R)-1-acetoxycryptotanshinone (1), (1R)-1-acetoxytanshinone IIA (2), and (15R)-1-oxoaegyptinone A (3)—as well as, new for this genus, isograndifoliol (4) were assessed. Three of these compounds exhibited profound inhibition of butyrylcholinesterase (BChE) and much weaker inhibition of acetylcholinesterase (AChE). All compounds (1–4) selectively inhibited BChE (IC50 = 2.4, 7.9, 50.8, and 0.9 µM, respectively), whereas only compounds 3 and 4 moderately inhibited AChE (IC50 329.8 µM and 342.9 µM). Molecular docking and in silico toxicology prediction studies were also performed on the active compounds. Natural oxygenated norditerpenoids from the traditional Central Asian medicinal plant P. atriplicifolia are selective BChE inhibitors. Their high potential makes them useful candidate molecules for further investigation as lead compounds in the development of a natural drug against dementia caused by neurodegenerative diseases.
The Toxicity and Polymorphism of β-Amyloid Oligomers
Authors: Huang Ya-ru , Liu Rui-tian
Published: June 2020

It is widely accepted that β-amyloid oligomers (Aβos) play a key role in the progression of Alzheimer’s disease (AD) by inducing neuron damage and cognitive impairment, but Aβos are highly heterogeneous in their size, structure and cytotoxicity, making the corresponding studies tough to carry out. Nevertheless, a number of studies have recently made remarkable progress in the describing the characteristics and pathogenicity of Aβos. We here review the mechanisms by which Aβos exert their neuropathogenesis for AD progression, including receptor binding, cell membrane destruction, mitochondrial damage, Ca2+ homeostasis dysregulation and tau pathological induction. We also summarize the characteristics and pathogenicity such as the size, morphology and cytotoxicity of dimers, trimers, Aβ*56 and spherical oligomers, and suggest that Aβos may play a different role at different phases of AD pathogenesis, resulting in differential consequences on neuronal synaptotoxicity and survival. It is warranted to investigate the temporal sequence of Aβos in AD human brain and examine the relationship between different Aβos and cognitive impairment.
The Telocytes: Ten Years after Their Introduction in the Scientific Literature. An Update on Their Morphology, Distribution, and Potential Roles in the Gut
Authors: Vannucchi Maria Giuliana
Published: June 2020

Ten years ago, the term ‘telocyte’ was introduced in the scientific literature to describe a ‘new’ cell type described in the connective tissue of several organs by Popescu and Faussone-Pellegrini (2010). Since then, 368 papers containing the term ‘telocyte’ have been published, 261 of them in the last five years. These numbers underscore the growing interest in this cell type in the scientific community and the general acceptance of the name telocyte to indicate this interstitial cell. Most of these studies, while confirming the importance of transmission electron microscopy to identify the telocytes with certainty, highlight the variability of their immune phenotypes. This variability was interpreted as due to (i) the ability of the telocytes to adapt to the different sites in which they reside; (ii) the distinct functions they are likely to perform; and (iii) the existence of telocyte subtypes. In the present paper, an overview of the last 10 years of literature on telocytes located in the gut will be attempted, confining the revision to the morphological findings. A distinct chapter will be dedicated to the recently hypothesized role of the telocytes the intestinal mucosa. Through this review, it will be shown that telocytes, despite their variability, are a unique interstitial cell.
Fructose and Uric Acid: Major Mediators of Cardiovascular Disease Risk Starting at Pediatric Age
Authors: Russo Elisa , Leoncini Giovanna , Esposito Pasquale , Garibotto Giacomo , Pontremoli Roberto , Viazzi Francesca
Published: June 2020

Recently, there has been a growing interest in epidemiological and clinical studies supporting a pathogenetic role of fructose in cardio-metabolic diseases, especially in children and adolescents. In the present review, we summarize experimental data on the potential biological mechanisms linking fructose and uric acid in the development of insulin resistance, metabolic syndrome, obesity, diabetes, hypertension, non-alcoholic fatty liver disease and chronic renal disease, thereby contributing to an increase in cardiovascular risk at pediatric age.
Human Erythrocytes Exposed to Phthalates and Their Metabolites Alter Antioxidant Enzyme Activity and Hemoglobin Oxidation
Authors: Sicińska Paulina , Kik Kinga , Bukowska Bożena
Published: June 2020

Phthalates used as plasticizers have become a part of human life because of their important role in various industries. Human exposure to these compounds is unavoidable, and therefore their mechanisms of toxicity should be investigated. Due to their structure and function, human erythrocytes are increasingly used as a cell model for testing the in vitro toxicity of various xenobiotics. Therefore, the purpose of our study was to assess the effect of selected phthalates on methemoglobin (metHb), reactive oxygen species (ROS) including hydroxyl radical levels, as well as the activity of antioxidative enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), in human erythrocytes. Erythrocytes were incubated with di-n-butyl phthalate (DBP), butylbenzyl phthalate (BBP), and their metabolites, i.e., mono-n-butyl phthalate (MBP) and monobenzyl phthalate (MBzP), at concentrations ranging from 0.5 to 100 µg/mL for 6 or 24 h. This study shows that the analyzed phthalates disturbed the redox balance in human erythrocytes. DBP and BBP, at much lower concentrations than their metabolites, caused a statistically significant increase of metHb and ROS, including hydroxyl radical levels, and changed the activity of antioxidant enzymes. The studied phthalates disturbed the redox balance in human erythrocytes, which may contribute to the accelerated removal of these cells from the circulation.
Modulation of DNA Damage Response by Sphingolipid Signaling: An Interplay that Shapes Cell Fate
Authors: Francis Marina , Abou Daher Alaa , Azzam Patrick , Mroueh Manal , Zeidan Youssef H.
Published: June 2020

Although once considered as structural components of eukaryotic biological membranes, research in the past few decades hints at a major role of bioactive sphingolipids in mediating an array of physiological processes including cell survival, proliferation, inflammation, senescence, and death. A large body of evidence points to a fundamental role for the sphingolipid metabolic pathway in modulating the DNA damage response (DDR). The interplay between these two elements of cell signaling determines cell fate when cells are exposed to metabolic stress or ionizing radiation among other genotoxic agents. In this review, we aim to dissect the mediators of the DDR and how these interact with the different sphingolipid metabolites to mount various cellular responses.
MicroRNA-5572 Is a Novel MicroRNA-Regulating SLC30A3 in Sporadic Amyotrophic Lateral Sclerosis
Authors: Kurita Hisaka , Yabe Saori , Ueda Tomoyuki , Inden Masatoshi , Kakita Akiyoshi , Hozumi Isao
Published: June 2020

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease caused by the loss of motor neurons. Although the pathogenesis of sporadic ALS (sALS) remains unclear, it has recently been suggested that disorders of microRNA (miRNA) may be involved in neurodegenerative conditions. The purpose of this study was to investigate miRNA levels in sALS and the target genes of miRNA. Microarray and real-time RT-PCR analyses revealed significantly-decreased levels of miR-139-5p and significantly increased levels of miR-5572 in the spinal cords of sALS patients compared with those in controls. We then focused on miR-5572, which has not been reported in ALS, and determined its target gene. By using TargetScan, we predicted SLC30A3 as the candidate target gene of miR-5572. In a previous study, we found decreased SLC30A3 levels in the spinal cords of sALS patients. We revealed that SLC30A3 was regulated by miR-5572. Taken together, these results demonstrate that the level of novel miRNA miR-5572 is increased in sALS and that SLC30A3 is one of the target genes regulated by miR-5572.
The Circulating Nucleic Acid Characteristics of Non-Metastatic Soft Tissue Sarcoma Patients
Authors: Eastley Nicholas , Sommer Aurore , Ottolini Barbara , Neumann Rita , Luo Jin-Li , Hastings Robert K. , McCulloch Thomas , Esler Claire P. , Shaw Jacqueline A. , Ashford Robert U. , Royle Nicola J.
Published: June 2020

Soft tissue sarcomas (STS) are rare, malignant tumours with a generally poor prognosis. Our aim was to explore the potential of cell free DNA (cfDNA) and circulating tumour DNA (ctDNA) analysis to track non-metastatic STS patients undergoing attempted curative treatment. The analysed cohort (n = 29) contained multiple STS subtypes including myxofibrosarcomas, undifferentiated pleomorphic sarcomas, leiomyosarcomas, and dedifferentiated liposarcomas amongst others. Perioperative cfDNA levels trended towards being elevated in patients (p = 0.07), although did not correlate with tumour size, grade, recurrence or subtype, suggesting a limited diagnostic or prognostic role. To characterise ctDNA, an amplicon panel covering three genes commonly mutated in STSs was first trialled on serial plasma collected from nine patients throughout follow-up. This approach only identified ctDNA in 2.5% (one in 40) of the analysed samples. Next custom-designed droplet digital PCR assays and Ion AmpliSeq™ panels were developed to track single nucleotide variants identified in patients’ STSs by whole exome sequencing (1–6 per patient). These approaches identified ctDNA in 17% of patients. Although ctDNA was identified before radiologically detectable recurrence in two cases, the absence of demonstrable ctDNA in 83% of cases highlights the need for much work before circulating nucleic acids can become a useful means to track STS patients.
Genome-Protecting Compounds as Potential Geroprotectors
Authors: Proshkina Ekaterina , Shaposhnikov Mikhail , Moskalev Alexey
Published: June 2020

Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increasing stress and age-related deterioration in the functioning of these mechanisms result in damage accumulation, overcoming the functional threshold. This leads to aging and the development of age-related diseases. There are several ways to counteract these changes: (1) prevention of DNA damage through stimulation of antioxidant and detoxification systems, as well as transition metal chelation; (2) regulation of DNA methylation, chromatin structure, non-coding RNA activity and prevention of nuclear architecture alterations; (3) improving DNA damage response and repair; (4) selective removal of damaged non-functional and senescent cells. In the article, we have reviewed data about the effects of various trace elements, vitamins, polyphenols, terpenes, and other phytochemicals, as well as a number of synthetic pharmacological substances in these ways. Most of the compounds demonstrate the geroprotective potential and increase the lifespan in model organisms. However, their genome-protecting effects are non-selective and often are conditioned by hormesis. Consequently, the development of selective drugs targeting genome protection is an advanced direction.
Characterization of the Biogenic Volatile Organic Compounds (BVOCs) and Analysis of the PR1 Molecular Marker in Vitis vinifera L. Inoculated with the Nematode Xiphinema index
Authors: Castorina Giulia , Grassi Flaminia , Consonni Gabriella , Vitalini Sara , Oberti Roberto , Calcante Aldo , Ferrari Enrico , Bononi Monica , Iriti Marcello
Published: June 2020

Upon pathogen attack, plants very quickly undergo rather complex physico-chemical changes, such as the production of new chemicals or alterations in membrane and cell wall properties, to reduce disease damages. An underestimated threat is represented by root parasitic nematodes. In Vitis vinifera L., the nematode Xiphinema index is the unique vector of Grapevine fanleaf virus, responsible for fanleaf degeneration, one of the most widespread and economically damaging diseases worldwide. The aim of this study was to investigate changes in the emission of biogenic volatile organic compounds (BVOCs) in grapevines attacked by X. index. BVOCs play a role in plant defensive mechanisms and are synthetized in response to biotic damages. In our study, the BVOC profile was altered by the nematode feeding process. We found a decrease in β-ocimene and limonene monoterpene emissions, as well as an increase in α-farnesene and α-bergamotene sesquiterpene emissions in nematode-treated plants. Moreover, we evaluated the PR1 gene expression. The transcript level of PR1 gene was higher in the nematode-wounded roots, while in the leaf tissues it showed a lower expression compared to control grapevines.
GM1 as Adjuvant of Innovative Therapies for Cystic Fibrosis Disease
Authors: Mancini Giulia , Loberto Nicoletta , Olioso Debora , Dechecchi Maria Cristina , Cabrini Giulio , Mauri Laura , Bassi Rosaria , Schiumarini Domitilla , Chiricozzi Elena , Lippi Giuseppe , Pesce Emanuela , Sonnino Sandro , Pedemonte Nicoletta , Tamanini Anna , Aureli Massimo
Published: June 2020

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is expressed at the apical plasma membrane (PM) of different epithelial cells. The most common mutation responsible for the onset of cystic fibrosis (CF), F508del, inhibits the biosynthesis and transport of the protein at PM, and also presents gating and stability defects of the membrane anion channel upon its rescue by the use of correctors and potentiators. This prompted a multiple drug strategy for F508delCFTR aimed simultaneously at its rescue, functional potentiation and PM stabilization. Since ganglioside GM1 is involved in the functional stabilization of transmembrane proteins, we investigated its role as an adjuvant to increase the effectiveness of CFTR modulators. According to our results, we found that GM1 resides in the same PM microenvironment as CFTR. In CF cells, the expression of the mutated channel is accompanied by a decrease in the PM GM1 content. Interestingly, by the exogenous administration of GM1, it becomes a component of the PM, reducing the destabilizing effect of the potentiator VX-770 on rescued CFTR protein expression/function and improving its stabilization. This evidence could represent a starting point for developing innovative therapeutic strategies based on the co-administration of GM1, correctors and potentiators, with the aim of improving F508del CFTR function.
Urobiome in Gender—Related Diversities of Bladder Cancer
Authors: Bilski Konrad , Dobruch Jakub , Kozikowski Mieszko , Skrzypczyk Michał A. , Oszczudłowski Maciej , Ostrowski Jerzy
Published: June 2020

Bladder cancer (BC) remains the most common malignancy of urinary tract. Sex-related differences in BC epidemiology, diagnosis, therapy, and outcomes have been reported. Throughout the recent years, extensive research has been devoted to genetic and molecular alterations in BC. Apart from the molecular background, another related concept which has been speculated to contribute to gender diversities in BC is the role of urinary pathogens in bladder carcinogenesis. Microbiome studies, fueled by the availability of high-throughput DNA-based techniques, have shown that perturbation in the microbiome is associated with various human diseases. The aim of this review is to comprehensively analyze the current literature according to sex-related differences in the microbiome composition in BC.
Antiangiogenic Targets for Glioblastoma Therapy from a Pre-Clinical Approach, Using Nanoformulations
Authors: Nery de Albuquerque Rego Gabriel , da Hora Alves Arielly , Penteado Nucci Mariana , Bustamante Mamani Javier , Anselmo de Oliveira Fernando , Gamarra Lionel Fernel
Published: June 2020

Glioblastoma (GBM) is the most aggressive tumor type whose resistance to conventional treatment is mediated, in part, by the angiogenic process. New treatments involving the application of nanoformulations composed of encapsulated drugs coupled to peptide motifs that direct drugs to specific targets triggered in angiogenesis have been developed to reach and modulate different phases of this process. We performed a systematic review with the search criterion (Glioblastoma OR Glioma) AND (Therapy OR Therapeutic) AND (Nanoparticle) AND (Antiangiogenic OR Angiogenesis OR Anti-angiogenic) in Pubmed, Scopus, and Cochrane databases, in which 312 articles were identified; of these, only 27 articles were included after selection and analysis of eligibility according to the inclusion and exclusion criteria. The data of the articles were analyzed in five contexts: the characteristics of the tumor cells; the animal models used to induce GBM for antiangiogenic treatment; the composition of nanoformulations and their physical and chemical characteristics; the therapeutic anti-angiogenic process; and methods for assessing the effects on antiangiogenic markers caused by therapies. The articles included in the review were heterogeneous and varied in practically all aspects related to nanoformulations and models. However, there was slight variance in the antiangiogenic effect analysis. CD31 was extensively used as a marker, which does not provide a view of the effects on the most diverse aspects involved in angiogenesis. Therefore, the present review highlighted the need for standardization between the different approaches of antiangiogenic therapy for the GBM model that allows a more effective meta-analysis and that helps in future translational studies.
Identification of Prognostic Organic Cation and Anion Transporters in Different Cancer Entities by In Silico Analysis
Authors: Edemir Bayram
Published: June 2020

The information derived from next generation sequencing technology allows the identification of deregulated genes, gene mutations, epigenetic modifications, and other genomic events that are associated with a given tumor entity. Its combination with clinical data allows the prediction of patients’ survival with a specific gene expression pattern. Organic anion transporters and organic cation transporters are important proteins that transport a variety of substances across membranes. They are also able to transport drugs that are used for the treatment of cancer and could be used to improve treatment. In this study, we have made use of publicly available data to analyze if the expression of organic anion transporters or organic cation transporters have a prognostic value for a given tumor entity. The expression of most organic cation transporters is prognostic favorable. Within the organic anion transporters, the ratio between favorable and unfavorable organic anion transporters is nearly equal for most tumor entities and only in liver cancer is the number of unfavorable genes two times higher compared to favorable genes. Within the favorable genes, UNC13B, and SFXN2 cover nine cancer types and in the same way, SLC2A1, PLS3, SLC16A1, and SLC16A3 within the unfavorable set of genes and could serve as novel target structures.
Colorectal Cancer Early Detection in Stool Samples Tracing CpG Islands Methylation Alterations Affecting Gene Expression
Authors: Vega-Benedetti Ana Florencia , Loi Eleonora , Moi Loredana , Orrù Sandra , Ziranu Pina , Pretta Andrea , Lai Eleonora , Puzzoni Marco , Ciccone Letizia , Casadei-Gardini Andrea , Cabras Francesco , Fortunato Federica , Restivo Angelo , Zorcolo Luigi , Scartozzi Mario , Zavattari Patrizia
Published: June 2020

Colorectal cancer (CRC) is a major cause of cancer mortality. Early diagnosis is relevant for its prevention and treatment. Since DNA methylation alterations are early events in tumourigenesis and can be detected in cell-free DNA, they represent promising biomarkers for early CRC diagnosis through non-invasive methods. In our previous work, we identified 74 early altered CpG islands (CGIs) associated with genes involved in cell cross-talking and cell signalling pathways. The aim of this work was to test whether methylation-based biomarkers could be detected in non-invasive matrices. Our results confirmed methylation alterations of GRIA4 and VIPR2 in CRC tissues, using MethyLight, as well as in stool samples, using a much more sensitive technique as droplet digital PCR. Furthermore, we analysed expression levels of selected genes whose promoter CGIs were hypermethylated in CRC, detecting downregulation at mRNA and protein levels in CRC tissue for GRIA4, VIPR2, SPOCK1 and SLC6A3. Most of these genes were already lowly expressed in colon normal tissues supporting the idea that cancer DNA methylation targets genes already barely expressed in the matched normal tissues. Our study suggests GRIA4 and VIPR2 as biomarkers for early CRC diagnosis using stool samples and confirms downregulation of genes hypermethylated in CRC.
Experimentally Determined Long Intrinsically Disordered Protein Regions Are Now Abundant in the Protein Data Bank
Authors: Monzon Alexander Miguel , Necci Marco , Quaglia Federica , Walsh Ian , Zanotti Giuseppe , Piovesan Damiano , Tosatto Silvio C. E.
Published: June 2020

Intrinsically disordered protein regions are commonly defined from missing electron density in X-ray structures. Experimental evidence for long disorder regions (LDRs) of at least 30 residues was so far limited to manually curated proteins. Here, we describe a comprehensive and large-scale analysis of experimental LDRs for 3133 unique proteins, demonstrating an increasing coverage of intrinsic disorder in the Protein Data Bank (PDB) in the last decade. The results suggest that long missing residue regions are a good quality source to annotate intrinsically disordered regions and perform functional analysis in large data sets. The consensus approach used to define LDRs allows to evaluate context dependent disorder and provide a common definition at the protein level.
The Regulation of CIN-like TCP Transcription Factors
Authors: Lan Jingqiu , Qin Genji
Published: June 2020

TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR 1 and 2 (TCP) family proteins are the plant-specific transcription factors extensively participating in diverse developmental processes by integrating external cues with internal signals. The roles of CINCINNATA (CIN)-like TCPs are conserved in control of the morphology and size of leaves, petal development, trichome formation and plant flowering. The tight regulation of CIN-like TCP activity at transcriptional and post-transcriptional levels are central for plant developmental plasticity in response to the ever-changing environmental conditions. In this review, we summarize recent progresses with regard to the function and regulation of CIN-like TCPs. CIN-like TCPs are regulated by abiotic and biotic cues including light, temperature and pathogens. They are also finely controlled by microRNA319 (miRNA319), chromatin remodeling complexes and auxin homeostasis. The protein degradation plays critical roles in tightly controlling the activity of CIN-like TCPs as well.
Correction: Xixi, Li., et al. The Plastidial Glyceraldehyde-3-Phosphate Dehydrogenase Is Critical for Abiotic Stress Response in Wheat. Int. J. Mol. Sci. 2019, 20, 1104
Authors: Li Xixi , Wei Wenjie , Li Fangfang , Zhang Lin , Deng Xia , Liu Ying , Yang Shushen
Published: June 2020

The author wishes to make the following correction to this paper [...]
Small Nucleolar RNAs Determine Resistance to Doxorubicin in Human Osteosarcoma
Authors: Godel Martina , Morena Deborah , Ananthanarayanan Preeta , Buondonno Ilaria , Ferrero Giulio , Hattinger Claudia M. , Di Nicolantonio Federica , Serra Massimo , Taulli Riccardo , Cordero Francesca , Riganti Chiara , Kopecka Joanna
Published: June 2020

Doxorubicin (Dox) is one of the most important first-line drugs used in osteosarcoma therapy. Multiple and not fully clarified mechanisms, however, determine resistance to Dox. With the aim of identifying new markers associated with Dox-resistance, we found a global up-regulation of small nucleolar RNAs (snoRNAs) in human Dox-resistant osteosarcoma cells. We investigated if and how snoRNAs are linked to resistance. After RT-PCR validation of snoRNAs up-regulated in osteosarcoma cells with different degrees of resistance to Dox, we overexpressed them in Dox-sensitive cells. We then evaluated Dox cytotoxicity and changes in genes relevant for osteosarcoma pathogenesis by PCR arrays. SNORD3A, SNORA13 and SNORA28 reduced Dox-cytotoxicity when over-expressed in Dox-sensitive cells. In these cells, GADD45A and MYC were up-regulated, TOP2A was down-regulated. The same profile was detected in cells with acquired resistance to Dox. GADD45A/MYC-silencing and TOP2A-over-expression counteracted the resistance to Dox induced by snoRNAs. We reported for the first time that snoRNAs induce resistance to Dox in human osteosarcoma, by modulating the expression of genes involved in DNA damaging sensing, DNA repair, ribosome biogenesis, and proliferation. Targeting snoRNAs or down-stream genes may open new treatment perspectives in chemoresistant osteosarcomas.