bluuebunny/crossref_metadata_2025 huggingface dataset:
Loop-Mediated Isothermal Amplification (LAMP): A Rapid, Sensitive, Specific, and Cost-Effective Point-of-Care Test for Coronaviruses in the Context of COVID-19 Pandemic
Authors: Augustine Robin , Hasan Anwarul , Das Suvarthi , Ahmed Rashid , Mori Yasuyoshi , Notomi Tsugunori , Kevadiya Bhavesh , Thakor Avnesh
Published: July 2020

The rampant spread of COVID-19 and the worldwide prevalence of infected cases demand a rapid, simple, and cost-effective Point of Care Test (PoCT) for the accurate diagnosis of this pandemic. The most common molecular tests approved by regulatory bodies across the world for COVID-19 diagnosis are based on Polymerase Chain Reaction (PCR). While PCR-based tests are highly sensitive, specific, and remarkably reliable, they have many limitations ranging from the requirement of sophisticated laboratories, need of skilled personnel, use of complex protocol, long wait times for results, and an overall high cost per test. These limitations have inspired researchers to search for alternative diagnostic methods that are fast, economical, and executable in low-resource laboratory settings. The discovery of Loop-mediated isothermal Amplification (LAMP) has provided a reliable substitute platform for the accurate detection of low copy number nucleic acids in the diagnosis of several viral diseases, including epidemics like Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). At present, a cocktail of LAMP assay reagents along with reverse transcriptase enzyme (Reverse Transcription LAMP, RT-LAMP) can be a robust solution for the rapid and cost-effective diagnosis for COVID-19, particularly in developing, and low-income countries. In summary, the development of RT-LAMP based diagnostic tools in a paper/strip format or the integration of this method into a microfluidic platform such as a Lab-on-a-chip may revolutionize the concept of PoCT for COVID-19 diagnosis. This review discusses the principle, technology and past research underpinning the success for using this method for diagnosing MERS and SARS, in addition to ongoing research, and the prominent prospect of RT-LAMP in the context of COVID-19 diagnosis.
Sialidase Activity in Human Blood Serum Has a Distinct Seasonal Pattern: A Pilot Study
Authors: Glanz Victor Y. , Kashirskikh Dmitry A. , Grechko Andrey V. , Yet Shaw-Fang , Sobenin Igor A. , Orekhov Alexander N.
Published: July 2020

Desialylation—loss of terminal sialic acid residues from glycoconjugates catalyzed by sialidases—is involved in many human diseases and is considered a key molecular event of atherosclerosis onset. Desialylated low-density lipoproteins with atherogenic properties have been detected in human blood previously. However, there is currently no consensus on the origin of desialylation activity in the bloodstream. Here, we suggest viral intervention as a possible explanation. In order to address our hypothesis, we studied seasonal patterns of blood serum sialidase enzymatic activity and designed an approach to detect and quantify viral sialidase genetic presence. Increased sialidase activity in autumn-winter combined with detectable levels of influenza virus sialidase mRNA suggests exogenous viral sialidase as a viable component of desialylation in human blood, providing new insights on the molecular background of atherogenesis.
Polyamine-Mediated Transcriptional Regulation of Enzymatic Antioxidative Response to Excess Soil Moisture during Early Seedling Growth in Soybean
Authors: Sidhu Gagandip K. , Tuan Pham Anh , Renault Sylvie , Daayf Fouad , Ayele Belay T.
Published: July 2020

This study examined the expression patterns of antioxidative genes and the activity of the corresponding enzymes in the excess moisture-stressed seedlings of soybean in response to seed treatment with polyamines, spermine (Spm) and spermidine (Spd). At the 4 day after planting (DAP) stage, the excess moisture impaired the embryo axis growth, and this effect is associated with the downregulation of superoxide dismutase (GmSOD1) expression and SOD activity in the cotyledon. Seed treatment with Spm reversed the effects of excess moisture on embryo axis growth partly through enhancing glutathione reductase (GR) activity, in both the cotyledon and embryo axis, although no effect on the GmGR expression level was evident. Excess moisture inhibited the shoot and root growth in 7 DAP seedlings, and this is associated with decreased activities of GR in the shoot and SOD in the root. The effect of excess moisture on shoot and root growth was reversed by seed treatment with Spd, and this was mediated by the increased activities of ascorbate peroxidase (APX), catalase (CAT) and GR in the shoot, and APX in the root, however, only GR in the shoot appears to be regulated transcriptionally. Root growth was also reversed by seed treatment with Spm with no positive effect on gene expression and enzyme activity.
Biochemical Profile of the Soybean Seed Embryonic Axis and Its Changes during Accelerated Aging
Authors: Ebone Luciano Antônio , Caverzan Andréia , Silveira Diógenes Cecchin , Siqueira Luciano de Oliveira , Lângaro Nadia Canali , Chiomento José Luís Trevizan , Chavarria Geraldo
Published: July 2020

Seed deterioration is an important topic in plant science, as the majority of cultivated species use seeds as their means of propagation; however, due to its complexity, the process of seed deterioration has not yet been completely elucidated. Three soybean cultivars (BMX Raio, BMX Zeus, and DM 53i54) exposed to four distinct periods of accelerated aging (0, 3, 6 and 9 days) in a fully randomized experimental design. Initially, vigor and germination tests were performed. The activity of superoxide dismutase, catalase, ascorbate peroxidase enzymes, hydrogen peroxide, malonaldehyde, DNA oxidation, macromolecules and mineral content, and Maillard reactions were quantified in the embryonic axis. Results showed that DNA did not suffer degradation or oxidation. In terms of consumption of reserves, only sugars were consumed, while levels of protein, starch, and triglycerides were maintained. The Maillard reaction did show potential as an indicator of buffer capacity of protein to ROS. Additionally, levels of catalase and ascorbate peroxidase decreased during the aging process. Moreover, nutrient analysis showed that a high magnesium level in the cultivar bestowed greater resilience to deterioration, which can indicate a potential function of magnesium in the cell structure via reflex in seed aging through seed respiration.
The Intersection of DNA Damage Response and Ferroptosis—A Rationale for Combination Therapeutics
Authors: Chen Po-Han , Tseng Watson Hua-Sheng , Chi Jen-Tsan
Published: July 2020

Ferroptosis is a novel form of iron-dependent cell death characterized by lipid peroxidation. While the importance and disease relevance of ferroptosis are gaining recognition, much remains unknown about its interaction with other biological processes and pathways. Recently, several studies have identified intricate and complicated interplay between ferroptosis, ionizing radiation (IR), ATM (ataxia–telangiectasia mutated)/ATR (ATM and Rad3-related), and tumor suppressor p53, which signifies the participation of the DNA damage response (DDR) in iron-related cell death. DDR is an evolutionarily conserved response triggered by various DNA insults to attenuate proliferation, enable DNA repairs, and dispose of cells with damaged DNA to maintain genome integrity. Deficiency in proper DDR in many genetic disorders or tumors also highlights the importance of this pathway. In this review, we will focus on the biological crosstalk between DDR and ferroptosis, which is mediated mostly via noncanonical mechanisms. For clinical applications, we also discuss the potential of combining ionizing radiation and ferroptosis-inducers for synergistic effects. At last, various ATM/ATR inhibitors under clinical development may protect ferroptosis and treat many ferroptosis-related diseases to prevent cell death, delay disease progression, and improve clinical outcomes.
Piggybacking on Classical Import and Other Non-Classical Mechanisms of Nuclear Import Appear Highly Prevalent within the Human Proteome
Authors: Tessier Tanner M. , MacNeil Katelyn M. , Mymryk Joe S.
Published: July 2020

One of the most conserved cellular pathways among eukaryotes is the extensively studied classical protein nuclear import pathway mediated by importin-α. Classical nuclear localization signals (cNLSs) are recognized by importin-α and are highly predictable due to their abundance of basic amino acids. However, various studies in model organisms have repeatedly demonstrated that only a fraction of nuclear proteins contain identifiable cNLSs, including those that directly interact with importin-α. Using data from the Human Protein Atlas and the Human Reference Interactome, and proteomic data from BioID/protein-proximity labeling studies using multiple human importin-α proteins, we determine that nearly 50% of the human nuclear proteome does not have a predictable cNLS. Surprisingly, between 25% and 50% of previously identified human importin-α cargoes do not have predictable cNLS. Analysis of importin-α cargo without a cNLS identified an alternative basic rich motif that does not resemble a cNLS. Furthermore, several previously suspected piggybacking proteins were identified, such as those belonging to the RNA polymerase II and transcription factor II D complexes. Additionally, many components of the mediator complex interact with at least one importin-α, yet do not have a predictable cNLS, suggesting that many of the subunits may enter the nucleus through an importin-α-dependent piggybacking mechanism.
α-Glucosidase Inhibitory Activity of Tannat Grape Phenolic Extracts in Relation to Their Ripening Stages
Authors: Dudoit Auriane , Benbouguerra Nawel , Richard Tristan , Hornedo-Ortega Ruth , Valls-Fonayet Josep , Coussot Gaëlle , Saucier Cédric
Published: July 2020

The present study aimed to screen grape extracts as novel α-glucosidase inhibitors to prevent type-2 diabetes and hyperglycemia. The total polyphenol content (TPC) was measured by Folin-Ciocalteu assay and the stilbene, anthocyanin and flavan-3-ol compounds were measured by Ultra High-Performance Liquid Chromatography coupled to Mass Spectrometry (UHPLC-MS). The α-glucosidase inhibitory of seed and skin Tannat grape extracts at four ripening stages were investigated. The highest TPC values were measured in seeds at the “veraison stage” (65.29 ± 5.33 g of Gallic Acid Equivalent (GAE) per kilogram of Fresh Weight (FW)). This was in accordance with the high flavan-3-ol contents measured for these two extracts (43.22 ± 2.59 and 45.45 ± 6.48 g/kg of seeds FW, respectively). The skin and seed extracts at the first stage of ripening exerted strong α-glucosidase inhibition, exceeding 95% (p < 0.05). A high linear correlation (R = 0.723, p ≤ 0.05) was observed between flavan-3-ol contents and the α-glucosidase inhibitory activity. The stilbene contents and this activity were moderately to strongly anti-correlated (R = –0.828, p ≤ 0.05 for trans-resveratrol). The enzyme kinetic studies revealed a mixed type of inhibition. This study brings promising results for the therapeutic potential of seed and skin Tannat grape extracts as a functional food product with anti-diabetic activity.
The UPR in Neurodegenerative Disease: Not Just an Inside Job
Authors: van Ziel Anna Maria , Scheper Wiep
Published: July 2020

Neurons are highly specialized cells that continuously and extensively communicate with other neurons, as well as glia cells. During their long lifetime, the post-mitotic neurons encounter many stressful situations that can disrupt protein homeostasis (proteostasis). The importance of tight protein quality control is illustrated by neurodegenerative disorders where disturbed neuronal proteostasis causes neuronal dysfunction and loss. For their unique function, neurons require regulated and long-distance transport of membrane-bound cargo and organelles. This highlights the importance of protein quality control in the neuronal endomembrane system, to which the unfolded protein response (UPR) is instrumental. The UPR is a highly conserved stress response that is present in all eukaryotes. However, recent studies demonstrate the existence of cell-type-specific aspects of the UPR, as well as cell non-autonomous UPR signaling. Here we discuss these novel insights in view of the complex cellular architecture of the brain and the implications for neurodegenerative diseases.
The Interaction of Bovine β-Lactoglobulin with Caffeic Acid: From Binding Mechanisms to Functional Complexes
Authors: Stănciuc Nicoleta , Râpeanu Gabriela , Bahrim Gabriela Elena , Aprodu Iuliana
Published: July 2020

In this study, the interaction of native and transglutaminase (Tgase) cross-linked β-lactoglobulin (β-LG) with caffeic acid (CA) was examined, aiming to obtain functional composites. Knowledge on the binding affinity and interaction mechanism was provided by performing fluorescence spectroscopy measurements, after heating the native and cross-linked protein at temperatures ranging from 25 to 95 °C. Regardless of the protein aggregation state, a static quenching mechanism of intrinsic fluorescence of β-LG by CA was established. The decrease of the Stern–Volmer constants with the temperature increase indicating the facile dissociation of the weakly bound complexes. The thermodynamic analysis suggested the existence of multiple contact types, such as Van der Waals’ force and hydrogen bonds, between β-LG and CA. Further molecular docking tests indicated the existence of various CA binding sites on the β-LG surface heat-treated at different temperatures. Anyway, regardless of the simulated temperature, the CA-β-LG assemblies appeared to be unstable. Compared to native protein, the CA-β-LG and CA-β-LGTgase complexes (ratio 1:1) exhibited significantly higher antioxidant activity and inhibitory effects on α-glucosidase, α-amylase, and pancreatic lipase, enzymes associated with metabolic syndrome. These findings might help the knowledge-based development of novel food ingredients with valuable biological properties.
A Novel Smad7 Genetic Variant Mapping on the Genomic Region Targeted by Mongersen Is Associated with Crohn’s Disease
Authors: Di Fusco Davide , Marafini Irene , Stolfi Carmine , Troncone Edoardo , Onali Sara , Lolli Elisabetta , Caprioli Flavio , Mazza Stefano , Raffaella Cascella , Manzo Laura , Borgiani Paola , Giuffrida Paolo , Di Sabatino Antonio , Monteleone Ivan , Monteleone Giovanni
Published: July 2020

Background: Down-regulation of Smad7 with a specific Smad7 antisense (AS) oligonucleotide-containing oral drug (Mongersen) was effective in pre-clinical studies and initial clinical trials in Crohn’s disease (CD) patients. A recent phase 3 trial was discontinued due to an apparent inefficacy of the drug, but factors contributing to the failure of this study remain unknown. Here, we analysed the frequency in CD of rs144204026 C/T single nucleotide polymorphism (SNP), which maps on the corresponding region targeted by the Smad7 AS contained in the Mongersen formulation and examined whether such a variant allele affects the ability of Smad7 AS to knockdown Smad7. Methods: rs144204026 SNP frequency was evaluated in two independent Italian cohorts of Crohn’s disease patients and normal controls. Genotyping was performed by allelic discrimination assay. Smad7 expression was evaluated in wild-type or heterozygous PBMCs treated with Smad7 AS. Results: No TT genotype was seen in CD patients and controls. Heterozygous genotype was more frequent in CD patients of both cohort 1 (11/235, 4.68%) and cohort 2 (8/122, 6.56%) as compared to controls (6/363, 1.65%; p = 0.029 and p = 0.01 respectively). Overall, a statistically significant association was observed between the T variant allele and CD patients’ susceptibility (p = 0.008; OR = 3.28, 95%CI: 1.3–8.3). Smad7 AS down-regulated Smad7 RNA independently of the presence of the variant allele. Conclusions: This is the first study to show an association between Smad7 rs144204026 SNP and CD patients. Data indicate that such a variant does not negatively influence the in vitro inhibitory effect of Smad7 AS on Smad7.
Gender-Related Differences in Trimethylamine and Oxidative Blood Biomarkers in Cardiovascular Disease Patients
Authors: Bordoni Laura , Fedeli Donatella , Piangerelli Marco , Pelikant-Malecka Iwona , Radulska Adrianna , Samulak Joanna J. , Sawicka Angelika K. , Lewicki Lukasz , Kalinowski Leszek , Olek Robert A. , Gabbianelli Rosita
Published: July 2020

Gender differences in the burden of cardiovascular disease (CVD) have been observed worldwide. In this study, plasmatic levels of trimethylamine (TMA) and blood oxidative biomarkers have been evaluated in 358 men (89 controls and 269 CVD patients) and 189 women (64 control and 125 CVD patients). The fluorescence technique was applied to determine erythrocyte membrane fluidity using 1,6-diphenyl-1,3,5-hexatriene (DPH) and Laurdan, while lipid hydroperoxides were assessed by diphenyl−1-pyrenylphosphine (DPPP). Results show that levels of plasmatic TMA were higher in healthy men with respect to healthy women (p = 0.0001). Significantly lower TMA was observed in male CVD patients (0.609 ± 0.104 μM) compared to healthy male controls (0.680 ± 0.118 μM) (p < 0.001), while higher levels of TMA were measured in female CVD patients (0.595 ± 0.115 μM) with respect to female controls (0.529 ± 0.073 μM) (p < 0.001). DPPP was significantly higher in healthy control men than in women (p < 0.001). Male CVD patients displayed a lower value of DPPP (2777 ± 1924) compared to healthy controls (5528 ± 2222) (p < 0.001), while no significant changes were measured in females with or without CVD (p > 0.05). Membrane fluidity was significantly higher (p < 0.001) in the hydrophobic bilayer only in control male subjects. In conclusion, gender differences were observed in blood oxidative biomarkers, and DPPP value might be suggested as a biomarker predictive of CVD only in men.
Synthesis and Biomedical Potential of Azapeptide Modulators of the Cluster of Differentiation 36 Receptor (CD36)
Authors: Proulx Caroline , Zhang Jinqiang , Sabatino David , Chemtob Sylvain , Ong Huy , Lubell William D.
Published: July 2020

The innovative development of azapeptide analogues of growth hormone releasing peptide-6 (GHRP-6) has produced selective modulators of the cluster of differentiation 36 receptor (CD36). The azapeptide CD36 modulators curb macrophage-driven inflammation and mitigate atherosclerotic and angiogenic pathology. In macrophages activated with Toll-like receptor-2 heterodimer agonist, they reduced nitric oxide production and proinflammatory cytokine release. In a mouse choroidal explant microvascular sprouting model, they inhibited neovascularization. In murine models of cardiovascular injury, CD36-selective azapeptide modulators exhibited cardioprotective and anti-atherosclerotic effects. In subretinal inflammation models, they altered activated mononuclear phagocyte metabolism and decreased immune responses to alleviate subsequent inflammation-dependent neuronal injury associated with retinitis pigmentosa, diabetic retinopathy and age-related macular degeneration. The translation of GHRP-6 to potent and selective linear and cyclic azapeptide modulators of CD36 is outlined in this review which highlights the relevance of turn geometry for activity and the biomedical potential of prototypes for the beneficial treatment of a wide range of cardiovascular, metabolic and immunological disorders.
Carbon-Coated Superparamagnetic Nanoflowers for Biosensors Based on Lateral Flow Immunoassays
Authors: Moyano Amanda , Serrano-Pertierra Esther , Salvador María , Martínez-García José , Piñeiro Yolanda , Yañez-Vilar Susana , Gónzalez-Gómez Manuel , Rivas José , Rivas Montserrat , Blanco-López M.
Published: July 2020

Superparamagnetic iron oxide nanoflowers coated by a black carbon layer (Fe3O4@C) were studied as labels in lateral flow immunoassays. They were synthesized by a one-pot solvothermal route, and they were characterized (size, morphology, chemical composition, and magnetic properties). They consist of several superparamagnetic cores embedded in a carbon coating holding carboxylic groups adequate for bioconjugation. Their multi-core structure is especially efficient for magnetic separation while keeping suitable magnetic properties and appropriate size for immunoassay reporters. Their functionality was tested with a model system based on the biotin–neutravidin interaction. For this, the nanoparticles were conjugated to neutravidin using the carbodiimide chemistry, and the lateral flow immunoassay was carried out with a biotin test line. Quantification was achieved with both an inductive magnetic sensor and a reflectance reader. In order to further investigate the quantifying capacity of the Fe3O4@C nanoflowers, the magnetic lateral flow immunoassay was tested as a detection system for extracellular vesicles (EVs), a novel source of biomarkers with interest for liquid biopsy. A clear correlation between the extracellular vesicle concentration and the signal proved the potential of the nanoflowers as quantifying labels. The limit of detection in a rapid test for EVs was lower than the values reported before for other magnetic nanoparticle labels in the working range 0–3 × 107 EVs/μL. The method showed a reproducibility (RSD) of 3% (n = 3). The lateral flow immunoassay (LFIA) rapid test developed in this work yielded to satisfactory results for EVs quantification by using a precipitation kit and also directly in plasma samples. Besides, these Fe3O4@C nanoparticles are easy to concentrate by means of a magnet, and this feature makes them promising candidates to further reduce the limit of detection.
Sniffing Out Urinary Tract Infection—Diagnosis Based on Volatile Organic Compounds and Smell Profile
Authors: Dospinescu Valentin-Mihai , Tiele Akira , Covington James
Published: July 2020

Current available methods for the clinical diagnosis of urinary tract infection (UTI) rely on a urine dipstick test or culturing of pathogens. The dipstick test is rapid (available in 1–2 min), but has a low positive predictive value, while culturing is time-consuming and delays diagnosis (24–72 h between sample collection and pathogen identification). Due to this delay, broad-spectrum antibiotics are often prescribed immediately. The over-prescription of antibiotics should be limited, in order to prevent the development of antimicrobial resistance. As a result, there is a growing need for alternative diagnostic tools. This paper reviews applications of chemical-analysis instruments, such as gas chromatography–mass spectrometry (GC-MS), selected ion flow tube mass spectrometry (SIFT-MS), ion mobility spectrometry (IMS), field asymmetric ion mobility spectrometry (FAIMS) and electronic noses (eNoses) used for the diagnosis of UTI. These methods analyse volatile organic compounds (VOCs) that emanate from the headspace of collected urine samples to identify the bacterial pathogen and even determine the causative agent’s resistance to different antibiotics. There is great potential for these technologies to gain wide-spread and routine use in clinical settings, since the analysis can be automated, and test results can be available within minutes after sample collection. This could significantly reduce the necessity to prescribe broad-spectrum antibiotics and allow the faster and more effective use of narrow-spectrum antibiotics.
Predictors of Depression in Caucasian Patients with Amyotrophic Lateral Sclerosis in Romania
Authors: Anca Motataianu , Sebastian Andone , Cristina Radu , Zoltan Bajko , Laura Barcutean , Adrian Balasa , Septimiu Voidazan , Adina Stoian , Smaranda Maier
Published: July 2020

Depression remains an underdiagnosed comorbidity which significantly decreases the quality of life in amyotrophic lateral sclerosis (ALS) patients. We aimed to investigate the prevalence of depression in a cohort of ALS patients with more than one year of disease evolution. A total of 50 ALS patients were evaluated with the Beck Depression Inventory II (BDI-II) and cognition, using the Mini-Cog Standardized Instrument (MCSI). The clinical disability was evaluated using the ALS Functional Rating Scale (ALSFRS). The prevalence of depression was 42.8%. A lower BDI-II score was significantly correlated with a higher education level, the spouse as a caregiver, spiritual devotion, and employment status (p < 0.05). A multiple linear regression analysis between the BDI-II score as the dependent variable and various independent variables such as spirituality, caregiver status, educational level, and occupational status revealed that only the type of caregiver (spouse or parent/child) significantly affected the BDI-II total score (p = 0.006). The functional disability significantly correlated with loss of appetite and loss of libido (p < 0.001). A high education, spiritual devotion, high ALSFRS, and the presence of the spouse as the caregiver were associated with the absence of depression.
Importance of Maximal Strength and Muscle-Tendon Mechanics for Improving Force Steadiness in Persons with Parkinson’s Disease
Authors: Smart Rowan R. , Richardson Cydney M. , Wile Daryl J. , Dalton Brian H. , Jakobi Jennifer M.
Published: July 2020

Although plantar flexion force steadiness (FS) is reduced in persons with Parkinson’s disease (PD), the underlying causes are unknown. The aim of this exploratory design study was to ascertain the influence of maximal voluntary contraction (MVC) force and gastrocnemius-Achilles muscle-tendon unit behaviour on FS in persons with PD. Nine persons with PD and nine age- and sex-matched non-PD controls (~70 years, 6 females per group) performed plantar flexion MVCs and sub-maximal tracking tasks at 5, 10, 25, 50 and 75% MVC. Achilles tendon elongation and medial gastrocnemius fascicle lengths were recorded via ultrasound during contraction. FS was quantified using the coefficient of variation (CV) of force. Contributions of MVC and tendon mechanics to FS were determined using multiple regression analyses. Persons with PD were 35% weaker during MVC (p = 0.04) and had 97% greater CV (p = 0.01) with 47% less fascicle shortening (p = 0.004) and 38% less tendon elongation (p = 0.002) than controls. Reduced strength was a direct contributor to lower FS in PD (ß = 0.631), and an indirect factor through limiting optimal muscle-tendon unit interaction. Interestingly, our findings indicate an uncoupling between fascicle shortening and tendon elongation in persons with PD. To better understand limitations in FS and muscle-tendon unit behavior, it is imperative to identify the origins of MVC decrements in persons with PD.
Facial Emotion Recognition in Children and Adolescents with Specific Learning Disorder
Authors: Operto Francesca Felicia , Pastorino Grazia Maria Giovanna , Stellato Maria , Morcaldi Lucia , Vetri Luigi , Carotenuto Marco , Viggiano Andrea , Coppola Giangennaro
Published: July 2020

Background: Some recent studies suggest that children and adolescents with different neurodevelopmental disorders perform worse in emotions recognition through facial expressions (ER) compared with typically developing peers. This impairment is also described in children with Specific Learning Disorders (SLD), compromising their scholastic achievement, social functioning, and quality of life. The purpose of our study is to evaluate ER skills in children and adolescents with SLD compared to a control group without learning disorders, and correlate them with intelligence and executive functions. Materials and Methods: Our work is a cross-sectional observational study. Sixty-three children and adolescents aged between 8 and 16 years, diagnosed with SLD, and 32 sex/age-matched controls without learning disorders were recruited. All participants were administered standardized neuropsychological tests, evaluating facial emotion recognition (NEPSY-II), executive functions (EpiTrack Junior), and intelligence profile (WISC-IV). Results: Emotion recognition mean score was significantly lower in the SLD group than in the controls group on the Mann–Whitney U test for unpaired samples (p < 0.001). The SLD group performed significantly lower than the control group in their abilities to identify neutral expressions, happiness, sadness, anger, and fear compared to controls (p < 0.001). ER scores were positively correlated to the executive functions scores. There was no correlation with the Total Intelligence Quotient scores but there is a significant positive correlation with Working Memory Index and Processing Speed Index measured by WISC.IV. Conclusion: Our study showed that children and adolescents with Specific Learning Disorders have facial emotion recognition impairment when compared with a group of peers without learning disorders. ER abilities were independent of their global intelligence but potentially related to executive functions.
Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs
Authors: Chizhikov Daniel , Buddington Randal K. , Iskusnykh Igor Y.
Published: July 2020

Preterm birth, a major contributor to infant mortality and morbidity, impairs development of the cerebellum, the brain region involved in cognitive processing and motor function. Previously, we showed that at term-equivalent age, preterm pigs that received formula supplemented with docosahexaenoic acid (DHA) esterified to phosphatidylserine (PS) had cerebellar weights similar to those of newborn term pigs and were heavier than control preterm pigs. However, whether PS-DHA promotes the development of specific cerebellar cell populations or enhances key developmental processes remains unknown. Here we investigated the effects of the PS-DHA on development of the cerebellum in preterm pigs delivered via caesarean section and reared for ten days on a milk replacer with either PS-DHA (experimental group) or sunflower oil (control group). Upon necropsy, key cerebellar populations were analyzed using immunohistochemistry. Consumption of PS-DHA was associated with the expansion of undifferentiated granule cell precursors and increased proliferation in the external granule cell layer (EGL). Preterm pigs that received PS-DHA also had significantly fewer apoptotic cells in the internal granule cell layer (IGL) that contains differentiated granule neurons. PS-DHA did not affect the number of differentiating granule cells in the inner EGL, thickness of the inner EGL, density of Purkinje cells, or Bergmann glial fibers, or diameter of Purkinje cells. Thus, PS-DHA may support cerebellar development in preterm subjects by enhancing proliferation of granule cells, a process specifically inhibited by preterm birth, and increasing the survival of granule cells in the IGL. These findings suggest that PS-DHA is a promising candidate for clinical studies directed at enhancing brain development.
Clinical and Pre-Clinical Evidence of Carbonic Anhydrase IX in Pancreatic Cancer and Its High Expression in Pre-Cancerous Lesions
Authors: Strapcova Sabina , Takacova Martina , Csaderova Lucia , Martinelli Paola , Lukacikova Lubomira , Gal Viliam , Kopacek Juraj , Svastova Eliska
Published: July 2020

Hypoxia is a common phenomenon that occurs in most solid tumors. Regardless of tumor origin, the evolution of a hypoxia-adapted phenotype is critical for invasive cancer development. Pancreatic ductal adenocarcinoma is also characterized by hypoxia, desmoplasia, and the presence of necrosis, predicting poor outcome. Carbonic anhydrase IX (CAIX) is one of the most strict hypoxia regulated genes which plays a key role in the adaptation of cancer cells to hypoxia and acidosis. Here, we summarize clinical data showing that CAIX expression is associated with tumor necrosis, vascularization, expression of Frizzled-1, mucins, or proteins involved in glycolysis, and inevitably, poor prognosis of pancreatic cancer patients. We also describe the transcriptional regulation of CAIX in relation to signaling pathways activated in pancreatic cancers. A large part deals with the preclinical evidence supporting the relevance of CAIX in processes leading to the aggressive behavior of pancreatic tumors. Furthermore, we focus on CAIX occurrence in pre-cancerous lesions, and for the first time, we describe CAIX expression within intraductal papillary mucinous neoplasia. Our review concludes with a detailed account of clinical trials implicating that treatment consisting of conventionally used therapies combined with CAIX targeting could result in an improved anti-cancer response in pancreatic cancer patients.
Chemosensitivity of Patient-Derived Cancer Stem Cells Identifies Colorectal Cancer Patients with Potential Benefit from FGFR Inhibitor Therapy
Authors: Yamamoto Takehito , Miyoshi Hiroyuki , Kakizaki Fumihiko , Maekawa Hisatsugu , Yamaura Tadayoshi , Morimoto Tomonori , Katayama Toshiro , Kawada Kenji , Sakai Yoshiharu , Taketo M. Mark
Published: July 2020

Some colorectal cancer patients harboring FGFR (fibroblast growth factor receptor) genetic alterations, such as copy number gain, mutation, and/or mRNA overexpression, were selected for enrollment in several recent clinical trials of FGFR inhibitor, because these genetic alterations were preclinically reported to be associated with FGFR inhibitor sensitivity as well as poor prognosis, invasiveness, and/or metastatic potential. However, few enrolled patients were responsive to FGFR inhibitors. Thus, practical strategies are eagerly awaited that can stratify patients for the subset that potentially responds to FGFR inhibitor chemotherapy. In the present study, we evaluated the sensitivity to FGFR inhibitor erdafitinib on 25 patient-derived tumor-initiating cell (TIC) spheroid lines carrying wild-type RAS and RAF genes, both in vitro and in vivo. Then, we assessed possible correlations between the sensitivity and the genetic/genomic data of the spheroid lines tested. Upon their exposure to erdafitinib, seven lines (7/25, 28%) responded significantly. Normal colonic epithelial stem cells were unaffected by the inhibitors. Moreover, the combination of erdafitinib with EGFR inhibitor erlotinib showed stronger growth inhibition than either drug alone, as efficacy was observed in 21 lines (84%) including 14 (56%) that were insensitive to erdafitinib alone. The in vitro erdafitinib response was accurately reflected on mouse xenografts of TIC spheroid lines. However, we found little correlation between their genetic/genomic alterations of TIC spheroids and the sensitivity to the FGFR inhibitor. Accordingly, we propose that direct testing of the patient-derived spheroids in vitro is one of the most reliable personalized methods in FGFR-inhibitor therapy of colorectal cancer patients.
Leukaemia Inhibitory Factor (LIF) Inhibits Cancer Stem Cells Tumorigenic Properties through Hippo Kinases Activation in Gastric Cancer
Authors: Seeneevassen Lornella , Giraud Julie , Molina-Castro Silvia , Sifré Elodie , Tiffon Camille , Beauvoit Clémentine , Staedel Cathy , Mégraud Francis , Lehours Philippe , Martin Océane C.B. , Boeuf Hélène , Dubus Pierre , Varon Christine
Published: July 2020

Cancer stem cells (CSCs) present chemo-resistance mechanisms contributing to tumour maintenance and recurrence, making their targeting of utmost importance in gastric cancer (GC) therapy. The Hippo pathway has been implicated in gastric CSC properties and was shown to be regulated by leukaemia inhibitory factor receptor (LIFR) and its ligand LIF in breast cancer. This study aimed to determine LIF’s effect on CSC properties in GC cell lines and patient-derived xenograft (PDX) cells, which remains unexplored. LIF’s treatment effect on CSC markers expression and tumoursphere formation was evaluated. The Hippo kinase inhibitor XMU-MP-1 and/or the JAK1 inhibitor Ruxolitinib were used to determine Hippo and canonical JAK/STAT pathway involvement in gastric CSCs’ response to LIF. Results indicate that LIF decreased tumorigenic and chemo-resistant CSCs, in both GC cell lines and PDX cells. In addition, LIF increased activation of LATS1/2 Hippo kinases, thereby decreasing downstream YAP/TAZ nuclear accumulation and TEAD transcriptional activity. LIF’s anti-CSC effect was reversed by XMU-MP-1 but not by Ruxolitinib treatment, highlighting the opposite effects of these two pathways downstream LIFR. In conclusion, LIF displays anti-CSC properties in GC, through Hippo kinases activation, and could in fine constitute a new CSCs-targeting strategy to help decrease relapse cases and bad prognosis in GC.
Src Family Tyrosine Kinases in Intestinal Homeostasis, Regeneration and Tumorigenesis
Authors: Sirvent Audrey , Mevizou Rudy , Naim Dana , Lafitte Marie , Roche Serge
Published: July 2020

Src, originally identified as an oncogene, is a membrane-anchored tyrosine kinase and the Src family kinase (SFK) prototype. SFKs regulate the signalling induced by a wide range of cell surface receptors leading to epithelial cell growth and adhesion. In the intestine, the SFK members Src, Fyn and Yes regulate epithelial cell proliferation and migration during tissue regeneration and transformation, thus implicating conserved and specific functions. In patients with colon cancer, SFK activity is a marker of poor clinical prognosis and a potent driver of metastasis formation. These tumorigenic activities are linked to SFK capacity to promote the dissemination and tumour-initiating capacities of epithelial tumour cells. However, it is unclear how SFKs promote colon tumour formation and metastatic progression because SFK-encoding genes are unfrequently mutated in human cancer. Here, we review recent findings on SFK signalling during intestinal homeostasis, regeneration and tumorigenesis. We also describe the key nongenetic mechanisms underlying SFK tumour activities in colorectal cancer, and discuss how these mechanisms could be exploited in therapeutic strategies to target SFK signalling in metastatic colon cancer.
PET Imaging Agents (FES, FFNP, and FDHT) for Estrogen, Androgen, and Progesterone Receptors to Improve Management of Breast and Prostate Cancers by Functional Imaging
Authors: Katzenellenbogen John A.
Published: July 2020

Many breast and prostate cancers are driven by the action of steroid hormones on their cognate receptors in primary tumors and in metastases, and endocrine therapies that inhibit hormone production or block the action of these receptors provide clinical benefit to many but not all of these cancer patients. Because it is difficult to predict which individuals will be helped by endocrine therapies and which will not, positron emission tomography (PET) imaging of estrogen receptor (ER) and progesterone receptor (PgR) in breast cancer, and androgen receptor (AR) in prostate cancer can provide useful, often functional, information on the likelihood of endocrine therapy response in individual patients. This review covers our development of three PET imaging agents, 16α-[18F]fluoroestradiol (FES) for ER, 21-[18F]fluoro-furanyl-nor-progesterone (FFNP) for PgR, and 16β-[18F]fluoro-5α-dihydrotestosterone (FDHT) for AR, and the evolution of their clinical use. For these agents, the pathway from concept through development tracks with an emerging understanding of critical performance criteria that is needed for successful PET imaging of these low-abundance receptor targets. Progress in the ongoing evaluation of what they can add to the clinical management of breast and prostate cancers reflects our increased understanding of these diseases and of optimal strategies for predicting the success of clinical endocrine therapies.
Gold Nanoparticles as a Potent Radiosensitizer: A Transdisciplinary Approach from Physics to Patient
Authors: Penninckx Sébastien , Heuskin Anne-Catherine , Michiels Carine , Lucas Stéphane
Published: July 2020

Over the last decade, a growing interest in the improvement of radiation therapies has led to the development of gold-based nanomaterials as radiosensitizer. Although the radiosensitization effect was initially attributed to a dose enhancement mechanism, an increasing number of studies challenge this mechanistic hypothesis and evidence the importance of chemical and biological contributions. Despite extensive experimental validation, the debate regarding the mechanism(s) of gold nanoparticle radiosensitization is limiting its clinical translation. This article reviews the current state of knowledge by addressing how gold nanoparticles exert their radiosensitizing effects from a transdisciplinary perspective. We also discuss the current and future challenges to go towards a successful clinical translation of this promising therapeutic approach.
Inhibition of the Lysophosphatidylinositol Transporter ABCC1 Reduces Prostate Cancer Cell Growth and Sensitizes to Chemotherapy
Authors: Emmanouilidi Aikaterini , Casari Ilaria , Gokcen Akkaya Begum , Maffucci Tania , Furic Luc , Guffanti Federica , Broggini Massimo , Chen Xi , Maxuitenko Yulia Y. , Keeton Adam B. , Piazza Gary A. , Linton Kenneth J. , Falasca Marco
Published: July 2020

Expression of ATP-binding cassette (ABC) transporters has long been implicated in cancer chemotherapy resistance. Increased expression of the ABCC subfamily transporters has been reported in prostate cancer, especially in androgen-resistant cases. ABCC transporters are known to efflux drugs but, recently, we have demonstrated that they can also have a more direct role in cancer progression. The pharmacological potential of targeting ABCC1, however, remained to be assessed. In this study, we investigated whether the blockade of ABCC1 affects prostate cancer cell proliferation using both in vitro and in vivo models. Our data demonstrate that pharmacological inhibition of ABCC1 reduced prostate cancer cell growth in vitro and potentiated the effects of Docetaxel in vitro and in mouse models of prostate cancer in vivo. Collectively, these data identify ABCC1 as a novel and promising target in prostate cancer therapy.
Correction: Gualdani, R.; et al. Store-Operated Calcium Entry Contributes to Cisplatin-Induced Cell Death in Non-Small Cell Lung Carcinoma. Cancers 2019, 11, 430
Authors: Gualdani Roberta , de Clippele Marie , Ratbi Ikram , Gailly Philippe , Tajeddine Nicolas
Published: July 2020

The authors wish to make the following corrections to this paper [...]
Regioselective Hydroxylation of Naringin Dihydrochalcone to Produce Neoeriocitrin Dihydrochalcone by CYP102A1 (BM3) Mutants
Authors: Nguyen Thi Huong Ha , Woo Su-Min , Nguyen Ngoc Anh , Cha Gun-Su , Yeom Soo-Jin , Kang Hyung-Sik , Yun Chul-Ho
Published: July 2020

Naringin dihydrochalcone (DC) is originally derived from the flavonoid naringin, which occurs naturally in citrus fruits, especially in grapefruit. It is used as an artificial sweetener with a strong antioxidant activity with potential applications in food and pharmaceutical fields. At present, enzymatic and chemical methods to make products of naringin DC by hydroxylation reactions have not been developed. Here, an enzymatic strategy for the efficient synthesis of potentially valuable products from naringin DC, a glycoside of phloretin, was developed using Bacillus megaterium CYP102A1 monooxygenase. The major product was identified to be neoeriocitrin DC by NMR and LC-MS analyses. Sixty-seven mutants of CYP102A1 were tested for hydroxylation of naringin DC to produce neoeriocitrin DC. Six mutants with high activity were selected to determine the kinetic parameters and total turnover numbers (TTNs). The kcat value of the most active mutant was 11 min−1 and its TTN was 315. The productivity of neoeriocitrin DC production increased up to 1.1 mM h−1, which corresponds to 0.65 g L−1 h−1. In this study, we achieved a regioselective hydroxylation of naringin DC to produce neoeriocitrin DC.
Plasmonic Photocatalysts for Microbiological Applications
Authors: Endo-Kimura Maya , Kowalska Ewa
Published: July 2020

Wide-bandgap semiconductors modified with nanostructures of noble metals for photocatalytic activity under vis irradiation due to localized surface plasmon resonance (LSPR), known as plasmonic photocatalysts, have been intensively investigated over the last decade. Most literature reports discuss the properties and activities of plasmonic photocatalysts for the decomposition of organic compounds and solar energy conversion. Although noble metals, especially silver and copper, have been known since ancient times as excellent antimicrobial agents, there are only limited studies on plasmonic photocatalysts for the inactivation of microorganisms (considering vis-excitation). Accordingly, this review has discussed the available literature reports on microbiological applications of plasmonic photocatalysis, including antibacterial, antiviral and antifungal properties, and also a novel study on other microbiological purposes, such as cancer treatment and drug delivery. Although some reports indicate high antimicrobial properties of these photocatalysts and their potential for medical/pharmaceutical applications, there is still a lack of comprehensive studies on the mechanism of their interactions with microbiological samples. Moreover, contradictory data have also been published, and thus more study is necessary for the final conclusions on the key-factor properties and the mechanisms of inactivation of microorganisms and the treatment of cancer cells.
miRTil: An Extensive Repository for Nile Tilapia microRNA Next Generation Sequencing Data
Authors: Bovolenta Luiz Augusto , Pinhal Danillo , Acencio Marcio Luis , Oliveira Arthur Casulli de , Moxon Simon , Martins Cesar , Lemke Ney
Published: July 2020

Nile tilapia is the third most cultivated fish worldwide and a novel model species for evolutionary studies. Aiming to improve productivity and contribute to the selection of traits of economic impact, biotechnological approaches have been intensively applied to species enhancement. In this sense, recent studies have focused on the multiple roles played by microRNAs (miRNAs) in the post-transcriptional regulation of protein-coding genes involved in the emergence of phenotypes with relevance for aquaculture. However, there is still a growing demand for a reference resource dedicated to integrating Nile Tilapia miRNA information, obtained from both experimental and in silico approaches, and facilitating the analysis and interpretation of RNA sequencing data. Here, we present an open repository dedicated to Nile Tilapia miRNAs: the “miRTil database”. The database stores data on 734 mature miRNAs identified in 11 distinct tissues and five key developmental stages. The database provides detailed information about miRNA structure, genomic context, predicted targets, expression profiles, and relative 5p/3p arm usage. Additionally, miRTil also includes a comprehensive pre-computed miRNA-target interaction network containing 4936 targets and 19,580 interactions.