bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions among Long Non-Coding RNAs and microRNAs Influence Disease Phenotype in Diabetes and Diabetic Kidney Disease
Authors: Srivastava Swayam Prakash , Goodwin Julie E. , Tripathi Pratima , Kanasaki Keizo , Koya Daisuke
Published: June 2021

Large-scale RNA sequencing and genome-wide profiling data revealed the identification of a heterogeneous group of noncoding RNAs, known as long noncoding RNAs (lncRNAs). These lncRNAs play central roles in health and disease processes in diabetes and cancer. The critical association between aberrant expression of lncRNAs in diabetes and diabetic kidney disease have been reported. LncRNAs regulate diverse targets and can function as sponges for regulatory microRNAs, which influence disease phenotype in the kidneys. Importantly, lncRNAs and microRNAs may regulate bidirectional or crosstalk mechanisms, which need to be further investigated. These studies offer the novel possibility that lncRNAs may be used as potential therapeutic targets for diabetes and diabetic kidney diseases. Here, we discuss the functions and mechanisms of actions of lncRNAs, and their crosstalk interactions with microRNAs, which provide insight and promise as therapeutic targets, emphasizing their role in the pathogenesis of diabetes and diabetic kidney disease
Identification and Structural Aspects of G-Quadruplex-Forming Sequences from the Influenza A Virus Genome
Authors: Tomaszewska Maria , Szabat Marta , Zielińska Karolina , Kierzek Ryszard
Published: June 2021

Influenza A virus (IAV) causes seasonal epidemics and sporadic pandemics, therefore is an important research subject for scientists around the world. Despite the high variability of its genome, the structure of viral RNA (vRNA) possesses features that remain constant between strains and are biologically important for virus replication. Therefore, conserved structural motifs of vRNA can represent a novel therapeutic target. Here, we focused on the presence of G-rich sequences within the influenza A/California/07/2009(H1N1) genome and their ability to form RNA G-quadruplex structures (G4s). We identified 12 potential quadruplex-forming sequences (PQS) and determined their conservation among the IAV strains using bioinformatics tools. Then we examined the propensity of PQS to fold into G4s by various biophysical methods. Our results revealed that six PQS oligomers could form RNA G-quadruplexes. However, three of them were confirmed to adopt G4 structures by all utilized methods. Moreover, we showed that these PQS motifs are present within segments encoding polymerase complex proteins indicating their possible role in the virus biology.
Outcomes of Deferoxamine Action on H2O2-Induced Growth Inhibition and Senescence Progression of Human Endometrial Stem Cells
Authors: Shatrova Alla , Burova Elena , Kharchenko Marianna , Smirnova Irina , Lyublinskaya Olga , Nikolsky Nikolay , Borodkina Aleksandra
Published: June 2021

Mesenchymal stem cells (MSCs) are broadly applied in regenerative therapy to replace cells that are lost or impaired during disease. The low survival rate of MSCs after transplantation is one of the major limitations heavily influencing the success of the therapy. Unfavorable microenvironments with inflammation and oxidative stress in the damaged regions contribute to MSCs loss. Most of the strategies developed to overcome this obstacle are aimed to prevent stress-induced apoptosis, with little attention paid to senescence—another common stress reaction of MSCs. Here, we proposed the strategy to prevent oxidative stress-induced senescence of human endometrial stem cells (hMESCs) based on deferoxamine (DFO) application. DFO prevented DNA damage and stress-induced senescence of hMESCs, as evidenced by reduced levels of reactive oxygen species, lipofuscin, cyclin D1, decreased SA-β-Gal activity, and improved mitochondrial function. Additionally, DFO caused accumulation of HIF-1α, which may contribute to the survival of H2O2-treated cells. Importantly, cells that escaped senescence due to DFO preconditioning preserved all the properties of the initial hMESCs. Therefore, once protecting cells from oxidative damage, DFO did not alter further hMESCs functioning. The data obtained may become the important prerequisite for development of a new strategy in regenerative therapy based on MSCs preconditioning using DFO.
Inherited Defects of the ASC-1 Complex in Congenital Neuromuscular Diseases
Authors: Meunier Justine , Villar-Quiles Rocio-Nur , Duband-Goulet Isabelle , Ferreiro Ana
Published: June 2021

Defects in transcriptional and cell cycle regulation have emerged as novel pathophysiological mechanisms in congenital neuromuscular disease with the recent identification of mutations in the TRIP4 and ASCC1 genes, encoding, respectively, ASC-1 and ASCC1, two subunits of the ASC-1 (Activating Signal Cointegrator-1) complex. This complex is a poorly known transcriptional coregulator involved in transcriptional, post-transcriptional or translational activities. Inherited defects in components of the ASC-1 complex have been associated with several autosomal recessive phenotypes, including severe and mild forms of striated muscle disease (congenital myopathy with or without myocardial involvement), but also cases diagnosed of motor neuron disease (spinal muscular atrophy). Additionally, antenatal bone fractures were present in the reported patients with ASCC1 mutations. Functional studies revealed that the ASC-1 subunit is a novel regulator of cell cycle, proliferation and growth in muscle and non-muscular cells. In this review, we summarize and discuss the available data on the clinical and histopathological phenotypes associated with inherited defects of the ASC-1 complex proteins, the known genotype–phenotype correlations, the ASC-1 pathophysiological role, the puzzling question of motoneuron versus primary muscle involvement and potential future research avenues, illustrating the study of rare monogenic disorders as an interesting model paradigm to understand major physiological processes.
Towards Profiling of the G-Quadruplex Targeting Drugs in the Living Human Cells Using NMR Spectroscopy
Authors: Krafčík Daniel , Ištvánková Eva , Džatko Šimon , Víšková Pavlína , Foldynová-Trantírková Silvie , Trantírek Lukáš
Published: June 2021

Recently, the 1H-detected in-cell NMR spectroscopy has emerged as a unique tool allowing the characterization of interactions between nucleic acid-based targets and drug-like molecules in living human cells. Here, we assess the application potential of 1H and 19F-detected in-cell NMR spectroscopy to profile drugs/ligands targeting DNA G-quadruplexes, arguably the most studied class of anti-cancer drugs targeting nucleic acids. We show that the extension of the original in-cell NMR approach is not straightforward. The severe signal broadening and overlap of 1H in-cell NMR spectra of polymorphic G-quadruplexes and their complexes complicate their quantitative interpretation. Nevertheless, the 1H in-cell NMR can be used to identify drugs that, despite strong interaction in vitro, lose their ability to bind G-quadruplexes in the native environment. The in-cell NMR approach is adjusted to a recently developed 3,5-bis(trifluoromethyl)phenyl probe to monitor the intracellular interaction with ligands using 19F-detected in-cell NMR. The probe allows dissecting polymorphic mixture in terms of number and relative populations of individual G-quadruplex species, including ligand-bound and unbound forms in vitro and in cellulo. Despite the probe’s discussed limitations, the 19F-detected in-cell NMR appears to be a promising strategy to profile G-quadruplex–ligand interactions in the complex environment of living cells.
Sodium Glucose Co-Transporter 2 Inhibitors Ameliorate Endothelium Barrier Dysfunction Induced by Cyclic Stretch through Inhibition of Reactive Oxygen Species
Authors: Li Xiaoling , Römer Gregor , Kerindongo Raphaela P. , Hermanides Jeroen , Albrecht Martin , Hollmann Markus W. , Zuurbier Coert J. , Preckel Benedikt , Weber Nina C.
Published: June 2021

SGLT-2i’s exert direct anti-inflammatory and anti-oxidative effects on resting endothelial cells. However, endothelial cells are constantly exposed to mechanical forces such as cyclic stretch. Enhanced stretch increases the production of reactive oxygen species (ROS) and thereby impairs endothelial barrier function. We hypothesized that the SGLT-2i’s empagliflozin (EMPA), dapagliflozin (DAPA) and canagliflozin (CANA) exert an anti-oxidative effect and alleviate cyclic stretch-induced endothelial permeability in human coronary artery endothelial cells (HCAECs). HCAECs were pre-incubated with one of the SGLT-2i’s (1 µM EMPA, 1 µM DAPA and 3 µM CANA) for 2 h, followed by 10% stretch for 24 h. HCAECs exposed to 5% stretch were considered as control. Involvement of ROS was measured using N-acetyl-l-cysteine (NAC). The sodium-hydrogen exchanger 1 (NHE1) and NADPH oxidases (NOXs) were inhibited by cariporide, or GKT136901, respectively. Cell permeability and ROS were investigated by fluorescence intensity imaging. Cell permeability and ROS production were increased by 10% stretch; EMPA, DAPA and CANA decreased this effect significantly. Cariporide and GKT136901 inhibited stretch-induced ROS production but neither of them further reduced ROS production when combined with EMPA. SGLT-2i’s improve the barrier dysfunction of HCAECs under enhanced stretch and this effect might be mediated through scavenging of ROS. Anti-oxidative effect of SGLT-2i’s might be partially mediated by inhibition of NHE1 and NOXs.
The Influence of VE-Cadherin on Adhesion and Incorporation of Breast Cancer Cells into Vascular Endothelium
Authors: Brock Thomas , Boudriot Elisabeth , Klawitter Anke , Großer Marianne , Nguyen Trang T. P. , Giebe Sindy , Klapproth Erik , Temme Achim , El-Armouche Ali , Breier Georg
Published: June 2021

During metastasis, cancer cells that originate from the primary tumor circulate in the bloodstream, extravasate, and form micrometastases at distant locations. Several lines of evidence suggest that specific interactions between cancer cells and endothelial cells, in particular tumor cell adhesion to the endothelium and transendothelial migration, play a crucial role in extravasation. Here we have studied the role of vascular endothelial (VE)-cadherin which is expressed aberrantly by breast cancer cells and might promote such interactions. By comparing different human breast cancer cell lines, we observed that the number of cancer cells that adhered to endothelium correlated with VE-cadherin expression levels. VE-cadherin silencing experiments confirmed that VE-cadherin enhances cancer cell adhesion to endothelial cells. However, in contrast, the number of cancer cells that incorporated into the endothelium was not dependent on VE-cadherin. Thus, it appears that cancer cell adhesion and incorporation are distinct processes that are governed by different molecular mechanisms. When cancer cells incorporated into the endothelial monolayer, they formed VE-cadherin positive contacts with endothelial cells. On the other hand, we also observed tumor cells that had displaced endothelial cells, reflecting either different modes of incorporation, or a temporal sequence where cancer cells first form contact with endothelial cells and then displace them to facilitate transmigration. Taken together, these results show that VE-cadherin promotes the adhesion of breast cancer cells to the endothelium and is involved in the initial phase of incorporation, but not their transmigration. Thus, VE-cadherin might be of relevance for therapeutic strategies aiming at preventing the metastatic spread of breast cancer cells.
Association of IgG1 Antibody Clearance with FcγRIIA Polymorphism and Platelet Count in Infliximab-Treated Patients
Authors: Thibault Gilles , Paintaud Gilles , Sung Hsueh , Lajoie Laurie , Louis Edouard ,   the GETAID, Desvignes Celine , Watier Hervé , Gouilleux-Gruart Valérie , Ternant David
Published: June 2021

The FcγRIIA/CD32A is mainly expressed on platelets, myeloid and several endothelial cells. Its affinity is considered insufficient for allowing significant binding of monomeric IgG, while its H131R polymorphism (histidine > arginine at position 131) influences affinity for multimeric IgG2. Platelet FcγRIIA has been reported to contribute to IgG-containing immune-complexe clearance. Given our finding that platelet FcγRIIA actually binds monomeric IgG, we investigated the role of platelets and FcγRIIA in IgG antibody elimination. We used pharmacokinetics analysis of infliximab (IgG1) in individuals with controlled Crohn’s disease. The influence of platelet count and FcγRIIA polymorphism was quantified by multivariate linear modelling. The infliximab half-life increased with R allele number (13.2, 14.4 and 15.6 days for HH, HR and RR patients, respectively). It decreased with increasing platelet count in R carriers: from ≈20 days (RR) and ≈17 days (HR) at 150 × 109/L, respectively, to ≈13 days (both HR and RR) at 350 × 109/L. Moreover, a flow cytometry assay showed that infliximab and monomeric IgG1 bound efficiently to platelet FcγRIIA H and R allotypes, whereas panitumumab and IgG2 bound poorly to the latter. We propose that infliximab (and presumably any IgG1 antibody) elimination is partly due to an unappreciated mechanism dependent on binding to platelet FcγRIIA, which is probably tuned by its affinity for IgG2.
Satellitome Analysis of Rhodnius prolixus, One of the Main Chagas Disease Vector Species
Authors: Montiel Eugenia E. , Panzera Francisco , Palomeque Teresa , Lorite Pedro , Pita Sebastián
Published: June 2021

The triatomine Rhodnius prolixus is the main vector of Chagas disease in countries such as Colombia and Venezuela, and the first kissing bug whose genome has been sequenced and assembled. In the repetitive genome fraction (repeatome) of this species, the transposable elements represented 19% of R. prolixus genome, being mostly DNA transposon (Class II elements). However, scarce information has been published regarding another important repeated DNA fraction, the satellite DNA (satDNA), or satellitome. Here, we offer, for the first time, extended data about satellite DNA families in the R. prolixus genome using bioinformatics pipeline based on low-coverage sequencing data. The satellitome of R. prolixus represents 8% of the total genome and it is composed by 39 satDNA families, including four satDNA families that are shared with Triatoma infestans, as well as telomeric (TTAGG)n and (GATA)n repeats, also present in the T. infestans genome. Only three of them exceed 1% of the genome. Chromosomal hybridization with these satDNA probes showed dispersed signals over the euchromatin of all chromosomes, both in autosomes and sex chromosomes. Moreover, clustering analysis revealed that most abundant satDNA families configured several superclusters, indicating that R. prolixus satellitome is complex and that the four most abundant satDNA families are composed by different subfamilies. Additionally, transcription of satDNA families was analyzed in different tissues, showing that 33 out of 39 satDNA families are transcribed in four different patterns of expression across samples.
Overview of the Genetic Diversity of African Macrotermes (Termitidae: Macrotermitinae) and Implications for Taxonomy, Ecology and Food Science
Authors: Egan Bronwyn , Nethavhani Zwannda , van Asch Barbara
Published: June 2021

Macrotermes termites play important ecological roles and are consumed by many communities as a delicacy and dietary complement throughout Africa. However, lack of reliable morphological characters has hampered studies of Macrotermes diversity in a wide range of scientific fields including ecology, phylogenetics and food science. In order to place our preliminary assessment of the diversity of Macrotermes in South Africa in context, we analysed a comprehensive dataset of COI sequences for African species including new and publicly available data. Phylogenetic reconstruction and estimates of genetic divergence showed a high level of incongruity between species names and genetic groups, as well as several instances of cryptic diversity. We identified three main clades and 17 genetic groups in the dataset. We propose that this structure be used as a background for future surveys of Macrotermes diversity in Africa, thus mitigating the negative impact of the present taxonomic uncertainties in the genus. The new specimens collected in Limpopo fell into four distinct genetic groups, suggesting that the region harbours remarkable Macrotermes diversity relative to other African regions surveyed in previous studies. This work shows that African Macrotermes have been understudied across the continent, and that the genus contains cryptic diversity undetectable by classic taxonomy. Furthermore, these results may inform future taxonomic revisions in Macrotermes, thus contributing to advances in termitology.
The Implications of the COVID-19 Pandemic on Religious Exercise: Preliminary Remarks
Authors: Madera Adelaide
Published: June 2021

Since 2020, the spread of COVID-19 has had an overwhelming impact not only on our personal lives, but also on domestic regulatory frameworks. Influential academics have strongly underlined that, in times of deep crisis, such as the current global health crisis, the long-term workability of legal systems is put to a severe test. In this period, in fact, the protection of health has been given priority, as a precondition that is orientating many current legal choices. Such an unprecedented health emergency has also raised a serious challenge in terms of fundamental rights and liberties. Several basic rights that normally enjoy robust protection under constitutional, supranational, and international guarantees, have experienced a devastating “suspension” for the sake of public health and safety, thus giving rise to a vigorous debate concerning whether and to what extent the pandemic emergency justifies limitations on fundamental rights. The present paper introduces the Special Issue on “The crisis of the religious freedom during the age of COVID-19 pandemic”. Taking as a starting point the valuable contributions of the participants in the Special Issue, it explores analogous and distinctive implications of the COVID-19 pandemic in different legal contexts and underlines the relevance of cooperation between religious and public actors to face a global health crisis.
Optimization of Properties for Alumina-Spinel Refractory Castables by CMA (CaO-MgO-Al2O3) Aggregates
Authors: Tang Hai , Li Chunxue , Gao Jianying , Touzo Bruno , Liu Chunfeng , Yuan Wenjie
Published: June 2021

Aiming at optimizing properties of alumina-spinel refractory castables, coarse corundum particles were replaced partially with the particles of a novel porous multi-component CMA (CaO-MgO-Al2O3) aggregate in the same size. Properties including the bulk density, apparent porosity, strength, slag corrosion resistance, thermal shock resistance and thermal fatigue resistance of alumina-spinel refractory castables containing CMA aggregates were evaluated contrastively. The results demonstrated that the incorporation of CMA aggregates can significantly improve thermal shock resistance and thermal fatigue resistance of castables, although companying with slight decrease in the bulk density and strength. Moreover, slag penetration resistance of castables can also be enhanced by CMA aggregates with appropriate particle size. The influence of CMA aggregates on properties of alumina-spinel refractory castables depended strongly on their particle size.
Material Databases and Validation in Modelling the Structure of Castings Using the Cellular Automaton Method
Authors: Hajkowski Jakub , Sika Robert , Rogalewicz Michał , Popielarski Paweł , Matysiak Waldemar , Legutko Stanislaw
Published: June 2021

The paper presents the scope of applicability and the usefulness of the method of predicting crystalline structure of castings using a commercially available system called Calcosoft CAFE. The influence of individual values of the parameters of the thermal model and the model predicting the structure (phenomenon of nucleation and crystal growth), and the method of interpretation of the results were identified. In simulation studies, it is important to use reliable and validated material database, under appropriate conditions. It is necessary to predict the properties of castings with a comprehensive, new and practical approach to modelling the formation of phase components of structure in terms of both macroscale and microscale phenomena (Multiscale and Multiphysics). Therefore, in this paper, the experimental-simulation validation of the CAFE code was undertaken. The tests were carried out on castings solidifying under various heat transfer conditions controlled by mould materials such as: a homogenous mould made of moulding sand, moulding sand with chill, and mould made of insulating mass with chill. These conditions directly influence the structure formation. The method of validation of the structure was determined in terms of its three parameters, i.e., the degree of refinement of the crystals, the location of the columnar-to-equiaxed transition zone—CET and the angle of the crystals. The above tests enabled to extend the content of databases, which often lack the necessary values of parameters used in modelling, e.g., crystallization of a specific alloy under given conditions (sand casting, chills or laser surface treatment). On this basis, the basics of correlating the simulation results on a micro- and macroscale were generalized, the limits of the application of individual parameters (mould, alloy materials) and their impact on the structure formation were determined. It resulted in the extension of the database for simulation calculations.
Simplified Determination of RHEED Patterns and Its Explanation Shown with the Use of 3D Computer Graphics
Authors: Kokosza Łukasz , Pawlak Jakub , Mitura Zbigniew , Przybylski Marek
Published: June 2021

The process of preparation of nanostructured thin films in high vacuum can be monitored with the help of reflection high energy diffraction (RHEED). However, RHEED patterns, both observed or recorded, need to be interpreted. The simplest approaches are based on carrying out the Ewald construction for a set of rods perpendicular to the crystal surface. This article describes how the utilization of computer graphics may be useful for realistic reproduction of experimental conditions, and then for carrying out the Ewald construction in a reciprocal 3D space. The computer software was prepared in the Java programing language. The software can be used to interpret real diffractions patterns for relatively flat surfaces, and thus it may be helpful in broad research practice.
Prediction Model of the Resulting Dimensions of Welded Stamped Parts
Authors: Kadnár Milan , Káčer Peter , Harničárová Marta , Valíček Jan , Gombár Mirek , Kušnerová Milena , Tóth František , Boržan Marian , Rusnák Juraj
Published: June 2021

The combination of stamping and subsequent welding of components is an important area of the automotive industry. Stamping inaccuracies affect the final size of the stamping and the welded part. In this article, we deal with a specific component that is produced by such a procedure and is also a common part of the geometry of a car. We focused on the possibility of using a negative phenomenon—deformation during welding—on the partial elimination of inaccuracies arising during stamping. Based on the planned experiment, we created a prediction model for the selected part and its production, with the help of which it is possible to determine suitable welding parameters for a specific dimension of the stamping and the required monitored dimension of the welded part. The article also includes the results of additional experimental measurements verifying the accuracy of the model and prediction maps for practice.
Salmon (Salmo salar) Side Streams as a Bioresource to Obtain Potential Antioxidant Peptides after Applying Pressurized Liquid Extraction (PLE)
Authors: de la Fuente Beatriz , Pallarés Noelia , Berrada Houda , Barba Francisco J.
Published: June 2021

The pressurized liquid extraction (PLE) technique was used to obtain protein extracts with antioxidant capacity from salmon muscle remains, heads, viscera, skin, and tailfins. A protein recovery percentage ≈28% was obtained for all samples except for viscera, which was ≈92%. These values represented an increase of 1.5–4.8-fold compared to stirring extraction (control). Different SDS-PAGE profiles in control and PLE extracts revealed that extraction conditions affected the protein molecular weight distribution of the obtained extracts. Both TEAC (Trolox equivalent antioxidant capacity) and ORAC (oxygen radical antioxidant capacity) assays showed an outstanding antioxidant activity for viscera PLE extract. Through liquid chromatography coupled with electrospray ionization triple time-of-flight (nanoESI qQTOF) mass spectrometry, 137 and 67 peptides were identified in control and PLE extracts from salmon viscera, respectively None of these peptides was found among the antioxidant peptides inputted in the BIOPEP-UMP database. However, bioinformatics analysis showed several antioxidant small peptides encrypted in amino acid sequences of viscera extracts, especially GPP (glycine-proline-proline) and GAA (glycine-alanine-alanine) for PLE extracts. Further research on the relationship between antioxidant activity and specific peptides from salmon viscera PLE extracts is required. In addition, the salmon side streams studied presented non-toxic levels of As, Hg, Cd, and Pb, as well as the absence of mycotoxins or related metabolites. Overall, these results confirm the feasible use of farmed salmon processing side streams as alternative sources of protein and bioactive compounds for human consumption.
Antitumor Profile of Carbon-Bridged Steroids (CBS) and Triterpenoids
Authors: Dembitsky Valery , Gloriozova Tatyana , Poroikov Vladimir
Published: June 2021

This review focuses on the rare group of carbon-bridged steroids (CBS) and triterpenoids found in various natural sources such as green, yellow-green, and red algae, marine sponges, soft corals, ascidians, starfish, and other marine invertebrates. In addition, this group of rare lipids is found in amoebas, fungi, fungal endophytes, and plants. For convenience, the presented CBS and triterpenoids are divided into four groups, which include: (a) CBS and triterpenoids containing a cyclopropane group; (b) CBS and triterpenoids with cyclopropane ring in the side chain; (c) CBS and triterpenoids containing a cyclobutane group; (d) CBS and triterpenoids containing cyclopentane, cyclohexane or cycloheptane moieties. For the comparative characterization of the antitumor profile, we have added several semi- and synthetic CBS and triterpenoids, with various additional rings, to identify possible promising sources for pharmacologists and the pharmaceutical industry. About 300 CBS and triterpenoids are presented in this review, which demonstrate a wide range of biological activities, but the most pronounced antitumor profile. The review summarizes biological activities both determined experimentally and estimated using the well-known PASS software. According to the data obtained, two-thirds of CBS and triterpenoids show moderate activity levels with a confidence level of 70 to 90%; however, one third of these lipids demonstrate strong antitumor activity with a confidence level exceeding 90%. Several CBS and triterpenoids, from different lipid groups, demonstrate selective action on different types of tumor cells such as renal cancer, sarcoma, pancreatic cancer, prostate cancer, lymphocytic leukemia, myeloid leukemia, liver cancer, and genitourinary cancer with varying degrees of confidence. In addition, the review presents graphical images of the antitumor profile of both individual CBS and triterpenoids groups and individual compounds.
Dermacozine N, the First Natural Linear Pentacyclic Oxazinophenazine with UV–Vis Absorption Maxima in the Near Infrared Region, along with Dermacozines O and P Isolated from the Mariana Trench Sediment Strain Dermacoccus abyssi MT 1.1T
Authors: Juhasz Bertalan , Pech-Puch Dawrin , Tabudravu Jioji N. , Cautain Bastien , Reyes Fernando , Jiménez Carlos , Kyeremeh Kwaku , Jaspars Marcel
Published: June 2021

Three dermacozines, dermacozines N–P (1–3), were isolated from the piezotolerant Actinomycete strain Dermacoccus abyssi MT 1.1T, which was isolated from a Mariana Trench sediment in 2006. Herein, we report the elucidation of their structures using a combination of 1D/2D NMR, LC-HRESI-MSn, UV–Visible, and IR spectroscopy. Further confirmation of the structures was achieved through the analysis of data from density functional theory (DFT)–UV–Visible spectral calculations and statistical analysis such as two tailed t-test, linear regression-, and multiple linear regression analysis applied to either solely experimental or to experimental and calculated 13C-NMR chemical shift data. Dermacozine N (1) bears a novel linear pentacyclic phenoxazine framework that has never been reported as a natural product. Dermacozine O (2) is a constitutional isomer of the known dermacozine F while dermacozine P (3) is 8-benzoyl-6-carbamoylphenazine-1-carboxylic acid. Dermacozine N (1) is unique among phenoxazines due to its near infrared (NIR) absorption maxima, which would make this compound an excellent candidate for research in biosensing chemistry, photodynamic therapy (PDT), opto-electronic applications, and metabolic mapping at the cellular level. Furthermore, dermacozine N (1) possesses weak cytotoxic activity against melanoma (A2058) and hepatocellular carcinoma cells (HepG2) with IC50 values of 51 and 38 μM, respectively.
Design, Syntheses, and Bioevaluations of Some Novel N2-Acryloylbenzohydrazides as Chemostimulants and Cytotoxic Agents
Authors: Lakhani Kinjal , Borrego Edgar A. , Cano Karla G. , Dimmock Jonathan R. , Aguilera Renato J. , Das Swagatika , Roayapalley Praveen K. , Sharma Rajendra K. , Das Umashankar
Published: June 2021

A series of novel N2-acryloylhydrazides 1a–m and a related series of compounds 6a–c were prepared as potential chemostimulants. In general, these compounds are cytotoxic to human HCT 116 colon cancer cells, as well as human MCF-7 and MDA-MB-231 breast cancer cell lines. A representative compound N1-(3,4-dimethoxyphenylcarbonyl)-N2-acryloylhydrazine 1m sensitized HCT 116 cells to the potent antineoplastic agent 3,5-bis(benzylidene)-4-piperidone 2a, and also to 5-fluorouracil. A series of compounds was prepared that incorporated some of the molecular features of 2a and related compounds with various N2-acryloylhydrazides in series 1. These compounds are potent cytotoxins. Two modes of action of representative compounds are the lowering of mitochondrial membrane potential and increasing the concentration of reactive oxygen species.
A Microfluidic Platform for Cavitation-Enhanced Drug Delivery
Authors: Grisanti Giulia , Caprini Davide , Sinibaldi Giorgia , Scognamiglio Chiara , Silvani Giulia , Peruzzi Giovanna , Casciola Carlo Massimo
Published: June 2021

An endothelial-lined blood vessel model is obtained in a PDMS (Polydimethylsiloxane) microfluidic system, where vascular endothelial cells are grown under physiological shear stress, allowing -like maturation. This experimental model is employed for enhanced drug delivery studies, aimed at characterising the increase in endothelial permeability upon microbubble-enhanced ultrasound-induced (USMB) cavitation. We developed a multi-step protocol to couple the optical and the acoustic set-ups, thanks to a 3D-printed insonation chamber, provided with direct optical access and a support for the US transducer. Cavitation-induced interendothelial gap opening is then analysed using a customised code that quantifies gap area and the relative statistics. We show that exposure to US in presence of microbubbles significantly increases endothelial permeability and that tissue integrity completely recovers within 45 min upon insonation. This protocol, along with the versatility of the microfluidic platform, allows to quantitatively characterise cavitation-induced events for its potential employment in clinics.
RNA Helicase DDX3: A Double-Edged Sword for Viral Replication and Immune Signaling
Authors: Hernández-Díaz Tomás , Valiente-Echeverría Fernando , Soto-Rifo Ricardo
Published: June 2021

DDX3 is a cellular ATP-dependent RNA helicase involved in different aspects of RNA metabolism ranging from transcription to translation and therefore, DDX3 participates in the regulation of key cellular processes including cell cycle progression, apoptosis, cancer and the antiviral immune response leading to type-I interferon production. DDX3 has also been described as an essential cellular factor for the replication of different viruses, including important human threats such HIV-1 or HCV, and different small molecules targeting DDX3 activity have been developed. Indeed, increasing evidence suggests that DDX3 can be considered not only a promising but also a viable target for anticancer and antiviral treatments. In this review, we summarize distinct functional aspects of DDX3 focusing on its participation as a double-edged sword in the host immune response and in the replication cycle of different viruses.
Type-2 Diabetes as a Risk Factor for Severe COVID-19 Infection
Authors: Norouzi Mahnaz , Norouzi Shaghayegh , Ruggiero Alistaire , Khan Mohammad S. , Myers Stephen , Kavanagh Kylie , Vemuri Ravichandra
Published: June 2021

The current outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed coronavirus disease 2019 (COVID-19), has generated a notable challenge for diabetic patients. Overall, people with diabetes have a higher risk of developing different infectious diseases and demonstrate increased mortality. Type 2 diabetes mellitus (T2DM) is a significant risk factor for COVID-19 progression and its severity, poor prognosis, and increased mortality. How diabetes contributes to COVID-19 severity is unclear; however, it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Using the envelope spike glycoprotein SARS-CoV-2, COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) receptors, a key protein expressed in metabolic organs and tissues such as pancreatic islets. Therefore, it has been suggested that diabetic patients are more susceptible to severe SARS-CoV-2 infections, as glucose metabolism impairments complicate the pathophysiology of COVID-19 disease in these patients. In this review, we provide insight into the COVID-19 disease complications relevant to diabetes and try to focus on the present data and growing concepts surrounding SARS-CoV-2 infections in T2DM patients.
Anti-Inflammatory and Anti-Diabetic Effect of Black Soybean Anthocyanins: Data from a Dual Cooperative Cellular System
Authors: Kim Jin-Nam , Han Sung Nim , Kim Hye-Kyeong
Published: June 2021

Obesity is characterized by elevated infiltration of macrophages into adipose tissue, leading to the development of insulin resistance. The black soybean seed coat is a rich source of anthocyanins with antioxidative and anti-inflammatory activities. This study investigated the effects of black soybean anthocyanin extract (BSAn) on obesity-induced oxidative stress, the inflammatory response, and insulin resistance in a coculture system of hypertrophied 3T3-L1 adipocytes and RAW264 macrophages. Coculture of adipocytes with macrophages increased the production of reactive oxygen species and inflammatory mediators and cytokines (NO, MCP-1, PGE2, TNFα, and IL-6) and the release of free fatty acids but reduced anti-inflammatory adiponectin secretion. BSAn treatment (12.5, 25, 50, and 100 μg/mL) alleviated the coculture-induced changes (p < 0.001) and inhibited coculture-induced activation of JNK and ERK signaling (p < 0.01). BSAn also blocked the migration of RAW264.7 macrophages toward 3T3-L1 adipocytes. In addition, treatment with BSAn increased PPARγ expression and glucose uptake in response to insulin in hypertrophied 3T3-L1 adipocyte and RAW264.7 macrophage coculture (p < 0.01). These results demonstrate that BSAn attenuates inflammatory responses and improves adipocyte metabolic function in the coculture of hypertrophied 3T3-L1 adipocytes and RAW264.7 macrophages, suggesting the effectiveness of BSAn for obesity-induced insulin resistance.
In Vitro and In Vivo Trypanocidal Efficacy of Synthesized Nitrofurantoin Analogs
Authors: Munsimbwe Linous , Seetsi Anna , Namangala Boniface , N’Da David D. , Inoue Noboru , Suganuma Keisuke
Published: June 2021

African trypanosomes cause diseases in humans and livestock. Human African trypanosomiasis is caused by Trypanosoma brucei rhodesiense and T. b. gambiense. Animal trypanosomoses have major effects on livestock production and the economy in developing countries, with disease management depending mainly on chemotherapy. Moreover, only few drugs are available and these have adverse effects on patients, are costly, show poor accessibility, and parasites develop drug resistance to them. Therefore, novel trypanocidal drugs are urgently needed. Here, the effects of synthesized nitrofurantoin analogs were evaluated against six species/strains of animal and human trypanosomes, and the treatment efficacy of the selected compounds was assessed in vivo. Analogs 11 and 12, containing 11- and 12-carbon aliphatic chains, respectively, showed the highest trypanocidal activity (IC50 < 0.34 µM) and the lowest cytotoxicity (IC50 > 246.02 µM) in vitro. Structure-activity relationship analysis suggested that the trypanocidal activity and cytotoxicity were related to the number of carbons in the aliphatic chain and electronegativity. In vivo experiments, involving oral treatment with nitrofurantoin, showed partial efficacy, whereas the selected analogs showed no treatment efficacy. These results indicate that nitrofurantoin analogs with high hydrophilicity are required for in vivo assessment to determine if they are promising leads for developing trypanocidal drugs.
Update on PET Tracer Development for Muscarinic Acetylcholine Receptors
Authors: Ozenil Marius , Aronow Jonas , Millard Marlon , Langer Thierry , Wadsak Wolfgang , Hacker Marcus , Pichler Verena
Published: June 2021

The muscarinic cholinergic system regulates peripheral and central nervous system functions, and, thus, their potential as a therapeutic target for several neurodegenerative diseases is undoubted. A clinically applicable positron emission tomography (PET) tracer would facilitate the monitoring of disease progression, elucidate the role of muscarinic acetylcholine receptors (mAChR) in disease development and would aid to clarify the diverse natural functions of mAChR regulation throughout the nervous system, which still are largely unresolved. Still, no mAChR PET tracer has yet found broad clinical application, which demands mAChR tracers with improved imaging properties. This paper reviews strategies of mAChR PET tracer design and summarizes the binding properties and preclinical evaluation of recent mAChR tracer candidates. Furthermore, this work identifies the current major challenges in mAChR PET tracer development and provides a perspective on future developments in this area of research.
Aspirin-Loaded Polymeric Films for Drug Delivery Systems: Comparison between Soaking and Supercritical CO2 Impregnation
Authors: Coutinho Isabela Trindade , Maia-Obi Lígia Passos , Champeau Mathilde
Published: June 2021

Polymeric implants loaded with drugs can overcome the disadvantages of oral or injection drug administration and deliver the drug locally. Several methods can load drugs into polymers. Herein, soaking and supercritical CO2 (scCO2) impregnation methods were employed to load aspirin into poly(l-lactic acid) (PLLA) and linear low-density polyethylene (LLDPE). Higher drug loadings (DL) were achieved with scCO2 impregnation compared to soaking and in a shorter time (3.4 ± 0.8 vs. 1.3 ± 0.4% for PLLA; and 0.4 ± 0.5 vs. 0.6 ± 0.5% for LLDPE), due to the higher swelling capacity of CO2. The higher affinity of aspirin explained the higher DL in PLLA than in LLDPE. Residual solvent was detected in LLDPE prepared by soaking, but within the FDA concentration limits. The solvents used in both methods acted as plasticizers and increased PLLA crystallinity. PLLA impregnated with aspirin exhibited faster hydrolysis in vitro due to the catalytic effect of aspirin. Finally, PLLA impregnated by soaking showed a burst release because of aspirin crystals on the PLLA surface, and released 100% of aspirin within 60 days, whereas the PLLA prepared with scCO2 released 60% after 74 days by diffusion and PLLA erosion. Hence, the scCO2 impregnation method is adequate for higher aspirin loadings and prolonged drug release.
Radiation-Induced Graft Immobilization (RIGI): Covalent Binding of Non-Vinyl Compounds on Polymer Membranes
Authors: Schmidt Martin , Zahn Stefan , Gehlhaar Florian , Prager Andrea , Griebel Jan , Kahnt Axel , Knolle Wolfgang , Konieczny Robert , Gläser Roger , Schulze Agnes
Published: June 2021

Radiation-induced graft immobilization (RIGI) is a novel method for the covalent binding of substances on polymeric materials without the use of additional chemicals. In contrast to the well-known radiation-induced graft polymerization (RIGP), RIGI can use non-vinyl compounds such as small and large functional molecules, hydrophilic polymers, or even enzymes. In a one-step electron-beam-based process, immobilization can be performed in a clean, fast, and continuous operation mode, as required for industrial applications. This study proposes a reaction mechanism using polyvinylidene fluoride (PVDF) and two small model molecules, glycine and taurine, in aqueous solution. Covalent coupling of single molecules is achieved by radical recombination and alkene addition reactions, with water radiolysis playing a crucial role in the formation of reactive solute species. Hydroxyl radicals contribute mainly to the immobilization, while solvated electrons and hydrogen radicals play a minor role. Release of fluoride is mainly induced by direct ionization of the polymer and supported by water. Hydrophobic chains attached to cations appear to enhance the covalent attachment of solutes to the polymer surface. Computational work is complemented by experimental studies, including X-ray photoelectron spectroscopy (XPS) and fluoride high-performance ion chromatography (HPIC).
Moisture Absorption Behavior and Adhesion Properties of GNP/Epoxy Nanocomposite Adhesives
Authors: Kong Nurziana , Khalil Nur Zalikha , Fricke Holger
Published: June 2021

In the current work, an attempt has been made to investigate the effect of Graphene Nanoplatelets (GNP) reinforcement to water absorption behavior and mechanical properties of adhesive bonding with epoxy. Epoxy adhesive with various GNP content (i.e., 0.0~2.0 wt%) was utilized to joint aluminum adherend subjected to various immersion periods (i.e., 0~60 days). Subsequently, the effect of GNP reinforcement on water uptake, water absorption rate and tensile shear strength was investigated. Depending on GNP content, two distinct behaviors in water uptake and moisture absorption rate have been observed; specimens with lower GNP content (0.5~1.0 wt%) have demonstrated increased/retention of water uptake and water absorption rate regardless of immersion period. Meanwhile, at higher GNP content (1.5~2.0 wt%), decreased water uptake and water absorption rate are generally observed. At similar GNP content, regardless of immersion periods, water immersed specimens generally demonstrate higher or retention of shear strength when compared to specimens at 0-day immersion period. These observations suggest that the relation between moisture absorption behavior and mechanical properties of GNP-reinforced adhesive with GNP content are rather complex which might be attributed to the interplay of several possible mechanisms.
Collagen–Alginate Composite Hydrogel: Application in Tissue Engineering and Biomedical Sciences
Authors: Hu Tingyu , Lo Amy C. Y.
Published: June 2021

Alginate (ALG), a polysaccharide derived from brown seaweed, has been extensively investigated as a biomaterial not only in tissue engineering but also for numerous biomedical sciences owing to its wide availability, good compatibility, weak cytotoxicity, low cost, and ease of gelation. Nevertheless, alginate lacks cell-binding sites, limiting long-term cell survival and viability in 3D culture. Collagen (Col), a major component protein found in the extracellular matrix (ECM), exhibits excellent biocompatibility and weak immunogenicity. Furthermore, collagen contains cell-binding motifs, which facilitate cell attachment, interaction, and spreading, consequently maintaining cell viability and promoting cell proliferation. Recently, there has been a growing body of investigations into collagen-based hydrogel trying to overcome the poor mechanical properties of collagen. In particular, collagen–alginate composite (CAC) hydrogel has attracted much attention due to its excellent biocompatibility, gelling under mild conditions, low cytotoxicity, controllable mechanic properties, wider availability as well as ease of incorporation of other biomaterials and bioactive agents. This review aims to provide an overview of the properties of alginate and collagen. Moreover, the application of CAC hydrogel in tissue engineering and biomedical sciences is also discussed.
Three Destinies of Solution-Processable Polymer Light-Emitting Diodes under Long-Time Operation
Authors: Udovytska Ruslana , Chulkin Pavel , Wypych-Puszkarz Aleksandra , Jung Jaroslaw
Published: June 2021

The article describes three different ways of polymer light-emitting diode (PLED) degradation, caused by damage of the protective layer. The electroluminescence and charge-transport properties of a completely encapsulated diode, the diodes with a leaky protective layer and diodes without encapsulation were compared under long-time exploitation. The studied devices incorporated Super Yellow light-emitting poly-(1,4-phenylenevinylene) PPV copolymer as an electroluminescence component, and (poly-(3,4-ethylenedioxythiophene)–poly-(styrene sulfonate) (PEDOT:PSS) as a charge-transport layer between the indium tin oxide (ITO) anode and aluminum–calcium cathode. To analyze the PLED degradation mechanism regarding charge transport, impedance spectroscopy was used. The values of resistance and capacitance of the internal layers revealed an effect of applied voltage on charge carrier injection and recombination. The factors responsible for the device degradation were analyzed on a macromolecular level by comparing the plots of voltage dependence of resistance and capacitance at different operation times elapsed.
The Life Cycle Assessment for Polylactic Acid (PLA) to Make It a Low-Carbon Material
Authors: Rezvani Ghomi Erfan Rezvani , Khosravi Fatemeh , Saedi Ardahaei Ali Saedi , Dai Yunqian , Neisiany Rasoul Esmaeely , Foroughi Firoozeh , Wu Min , Das Oisik , Ramakrishna Seeram
Published: June 2021

The massive plastic production worldwide leads to a global concern for the pollution made by the plastic wastes and the environmental issues associated with them. One of the best solutions is replacing the fossil-based plastics with bioplastics. Bioplastics such as polylactic acid (PLA) are biodegradable materials with less greenhouse gas (GHG) emissions. PLA is a biopolymer produced from natural resources with good mechanical and chemical properties, therefore, it is used widely in packaging, agriculture, and biomedical industries. PLA products mostly end up in landfills or composting. In this review paper, the existing life cycle assessments (LCA) for PLA were comprehensively reviewed and classified. According to the LCAs, the energy and materials used in the whole life cycle of PLA were reported. Finally, the GHG emissions of PLA in each stage of its life cycle, including feedstock acquisition and conversion, manufacturing of PLA products, the PLA applications, and the end of life (EoL) options, were described. The most energy-intensive stage in the life cycle of PLA is its conversion. By optimizing the conversion process of PLA, it is possible to make it a low-carbon material with less dependence on energy sources.