bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Blood Coagulation Parameters and ADMA, NO, IL-6, and IL-18 Serum Levels in Patients with Neovascular AMD before, during, and after the Initial Loading Phase of Intravitreal Aflibercept
Authors: Wiciński Michał , Seredyka-Burduk Małgorzata , Liberski Sławomir , Marczak Daria , Pol Magdalena , Malinowski Bartosz , Pawlak-Osińska Katarzyna , Kaluzny Bartlomiej J.
Published: May 2021

We evaluated the effect of intravitreal injections of aflibercept (IVA) on blood coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT), as well as asymmetric dimethylarginine (ADMA), nitric oxide (NO), interleukin 6 (IL-6), and interleukin 18 (IL-18) serum levels in patients with neovascular AMD (nAMD). Twenty-two eyes of 22 patients with nAMD were included. Parameters were evaluated before and 2–3 days after the first IVA injection, and then immediately before and 2–3 days after the third IVA injection. We revealed prolongation of the TT after the initial loading phase of IVA (p = 0.041) and a significant increase in IL-18 serum concentration immediately before the third IVA administration compared to baseline (p = 0.037). There were no statistically significant differences of other parameters and PT, APTT, ADMA, NO, and IL-6 values remained within the normal range at each of the time points of the study. Our results suggest that repeated IVA administration may affect the common blood coagulation pathway, which manifests as a prolongation of the TT value. Furthermore, we showed a significant increase in serum concentration of the pro-inflammatory cytokineIL-18during the initial loading phase of IVA.
An Unsupervised Algorithm for Host Identification in Flaviviruses
Authors: Truong Nguyen Phuoc , Garcia-Vallvé Santiago , Puigbò Pere
Published: May 2021

Early characterization of emerging viruses is essential to control their spread, such as the Zika Virus outbreak in 2014. Among other non-viral factors, host information is essential for the surveillance and control of virus spread. Flaviviruses (genus Flavivirus), akin to other viruses, are modulated by high mutation rates and selective forces to adapt their codon usage to that of their hosts. However, a major challenge is the identification of potential hosts for novel viruses. Usually, potential hosts of emerging zoonotic viruses are identified after several confirmed cases. This is inefficient for deterring future outbreaks. In this paper, we introduce an algorithm to identify the host range of a virus from its raw genome sequences. The proposed strategy relies on comparing codon usage frequencies across viruses and hosts, by means of a normalized Codon Adaptation Index (CAI). We have tested our algorithm on 94 flaviviruses and 16 potential hosts. This novel method is able to distinguish between arthropod and vertebrate hosts for several flaviviruses with high values of accuracy (virus group 91.9% and host type 86.1%) and specificity (virus group 94.9% and host type 79.6%), in comparison to empirical observations. Overall, this algorithm may be useful as a complementary tool to current phylogenetic methods in monitoring current and future viral outbreaks by understanding host–virus relationships.
Does Compression Sensory Axonopathy in the Proximal Tibia Contribute to Noncontact Anterior Cruciate Ligament Injury in a Causative Way?—A New Theory for the Injury Mechanism
Authors: Sonkodi Balázs , Bardoni Rita , Hangody László , Radák Zsolt , Berkes István
Published: May 2021

Anterior cruciate ligament injury occurs when the ligament fibers are stretched, partially torn, or completely torn. The authors propose a new injury mechanism for non-contact anterior cruciate ligament injury of the knee. Accordingly, non-contact anterior cruciate ligament injury could not happen without the acute compression microinjury of the entrapped peripheral proprioceptive sensory axons of the proximal tibia. This would occur under an acute stress response when concomitant microcracks-fractures in the proximal tibia evolve due to the same excessive and repetitive compression forces. The primary damage may occur during eccentric contractions of the acceleration and deceleration moments of strenuous or unaccustomed fatiguing exercise bouts. This primary damage is suggested to be an acute compression/crush axonopathy of the proprioceptive sensory neurons in the proximal tibia. As a result, impaired proprioception could lead to injury of the anterior cruciate ligament as a secondary damage, which is suggested to occur during the deceleration phase. Elevated prostaglandin E2, nitric oxide and glutamate may have a critical neuro-modulatory role in the damage signaling in this dichotomous neuronal injury hypothesis that could lead to mechano-energetic failure, lesion and a cascade of inflammatory events. The presynaptic modulation of the primary sensory axons by the fatigued and microdamaged proprioceptive sensory fibers in the proximal tibia induces the activation of N-methyl-D-aspartate receptors in the dorsal horn of the spinal cord, through a process that could have long term relevance due to its contribution to synaptic plasticity. Luteinizing hormone, through interleukin-1β, stimulates the nerve growth factor-tropomyosin receptor kinase A axis in the ovarian cells and promotes tropomyosin receptor kinase A and nerve growth factor gene expression and prostaglandin E2 release. This luteinizing hormone induced mechanism could further elevate prostaglandin E2 in excess of the levels generated by osteocytes, due to mechanical stress during strenuous athletic moments in the pre-ovulatory phase. This may explain why non-contact anterior cruciate ligament injury is at least three-times more prevalent among female athletes.
Kaempferol-3-O-Glucuronide Ameliorates Non-Alcoholic Steatohepatitis in High-Cholesterol-Diet-Induced Larval Zebrafish and HepG2 Cell Models via Regulating Oxidation Stress
Authors: Deng Yang , Ma Ji , Weng Xin , Wang Yuqin , Li Maoru , Yang Tingting , Dou Zhiyang , Yin Zhiqi , Shang Jing
Published: May 2021

NAFLD (non-alcoholic fatty liver disease) is one of the most prominent liver diseases in the world. As a metabolic-related disease, the development of NAFLD is closely associated with various degrees of lipid accumulation, oxidation, inflammation, and fibrosis. Ilex chinensis Sims is a form of traditional Chinese medicine which is used to treat bronchitis, burns, pneumonia, ulceration, and chilblains. Kaempferol-3-O-glucuronide (K3O) is a natural chemical present in Ilex chinensis Sims. This study was designed to investigate the antioxidative, fat metabolism-regulating, and anti-inflammatory potential of K3O. A high-cholesterol diet (HCD) was used to establish steatosis in larval zebrafish, whereby 1mM free fatty acid (FFA) was used to induce lipid accumulation in HepG2 cells, while H2O2 was used to induce oxidative stress in HepG2. The results of this experiment showed that K3O reduced lipid accumulation and the level of reactive oxygen species (ROS) both in vivo (K3O, 40 μM) and in vitro (K3O, 20 μM). Additionally, K3O (40 μM) reduced neutrophil aggregation in vivo. K3O (20 μM) also decreased the level of malondialdehyde (MDA) and significantly increased the level of glutathione peroxidase (GSH-px) in both the HCD-induced larval zebrafish model and H2O2-exposed HepG2 cells. In the mechanism study, keap1, nrf2, tnf-α, and il-6 mRNA were all significantly reversed by K3O (20 μM) in zebrafish. Changes in Keap1 and Nrf2 mRNA expression were also detected in H2O2-exposed HepG2 cells after they were treated with K3O (20 μM). In conclusion, K3O exhibited a reduction in oxidative stress and lipid peroxidation, and this may be related to the Nrf2/Keap1 pathway in the NAFLD larval zebrafish model.
Optimization of Manufacturing Parameters and Tensile Specimen Geometry for Fused Deposition Modeling (FDM) 3D-Printed PETG
Authors: Özen Arda , Auhl Dietmar , Völlmecke Christina , Kiendl Josef , Abali Bilen Emek
Published: May 2021

Additive manufacturing provides high design flexibility, but its use is restricted by limited mechanical properties compared to conventional production methods. As technology is still emerging, several approaches exist in the literature for quantifying and improving mechanical properties. In this study, we investigate characterizing materials’ response of additive manufactured structures, specifically by fused deposition modeling (FDM). A comparative analysis is achieved for four different tensile test specimens for polymers based on ASTM D3039 and ISO 527-2 standards. Comparison of specimen geometries is studied with the aid of computations based on the Finite Element Method (FEM). Uniaxial tensile tests are carried out, after a careful examination of different slicing approaches for 3D printing. We emphasize the effects of the chosen slicer parameters on the position of failures in the specimens and propose a simple formalism for measuring effective mechanical properties of 3D-printed structures.
Definition and Utilization of the Null Controllable Region for Model Predictive Control of Multi-Input Linear Systems
Authors: Battista Angela , Mhaskar Prashant
Published: May 2021

The problem of guaranteeing stability from the entire null controllable region (NCR) for multi-input linear dynamical systems is addressed in the present manuscript. The proposed controller design is inspired by results for single input systems and generalized to multiple input systems. The approach relies on utilizing the level sets of the NCR as level sets of a Lyapunov function. A contractive constraint is incorporated into a model predictive control design, guaranteeing feasibility for any horizon length, and resulting in the NCR as the closed-loop stability region. The proposed method is illustrated using a simulation example.
New Oscillation Theorems for Second-Order Differential Equations with Canonical and Non-Canonical Operator via Riccati Transformation
Authors: Santra Shyam Sundar , Sethi Abhay Kumar , Moaaz Osama , Khedher Khaled Mohamed , Yao Shao-Wen
Published: May 2021

In this work, we prove some new oscillation theorems for second-order neutral delay differential equations of the form (a(ξ)((v(ξ)+b(ξ)v(ϑ(ξ)))′))′+c(ξ)G1(v(κ(ξ)))+d(ξ)G2(v(ς(ξ)))=0 under canonical and non-canonical operators, that is, ∫ξ0∞dξa(ξ)=∞ and ∫ξ0∞dξa(ξ)<∞. We use the Riccati transformation to prove our main results. Furthermore, some examples are provided to show the effectiveness and feasibility of the main results.
The Impact of Regulatory Reforms on Demand Weighted Average Prices
Authors: Tashpulatov Sherzod N.
Published: May 2021

Average prices are popularly used in the literature on price modeling. Calculating daily or weekly prices as an average over hourly or half-hourly trading periods assumes the same weight ignoring demand or traded volumes during those periods. Analyzing demand weighted average prices is important if producers may affect prices by decreasing them during low-demand periods and increasing them during high-demand periods within a day. The prediction of this price manipulation might have motivated the regulatory authority to introduce price caps not only on annual average prices but also on annual demand weighted average prices in the England and Wales wholesale electricity market. The dynamics of demand weighted average prices of electricity has been analyzed little in the literature. We show that skew generalized error distribution (SGED) is the appropriate assumption for model residuals. The estimated volatility model is used for evaluating the impact of regulatory reforms on demand weighted average prices during the complete history of the England and Wales wholesale electricity market.
Integrating Semilinear Wave Problems with Time-Dependent Boundary Values Using Arbitrarily High-Order Splitting Methods
Authors: Alonso-Mallo Isaías , Portillo Ana M.
Published: May 2021

The initial boundary-value problem associated to a semilinear wave equation with time-dependent boundary values was approximated by using the method of lines. Time integration is achieved by means of an explicit time method obtained from an arbitrarily high-order splitting scheme. We propose a technique to incorporate the boundary values that is more accurate than the one obtained in the standard way, which is clearly seen in the numerical experiments. We prove the consistency and convergence, with the same order of the splitting method, of the full discretization carried out with this technique. Although we performed mathematical analysis under the hypothesis that the source term was Lipschitz-continuous, numerical experiments show that this technique works in more general cases.
A Mathematical Approach to Law and Deal Modelling: Legislation and Agreements
Authors: Benito-Ostolaza Juan M. , Campión María J. , Estevan Asier
Published: May 2021

Social norms are a set of rules to be followed by the people of a community in order to have a better coexistence, to which the behaviors, tasks, and activities of the human being must be adjusted. The set or system of norms, rules, or duties regulates the actions of individuals among themselves. This work presents a new and original approach to the situations of agreement as well as to the constructions of regulations. This is done by giving a mathematical formalization to the set of all possible agreements or regulations, so that, then, the proximity between them is defined by means of a premetric. Thanks to this mathematical structure that tries to capture the problematic of agreements and modifications of regulations, some currently issues related to game theory or law are now reduced to mathematical optimization problems.
Conservative Approach in the Management of Large Periapical Cyst-Like Lesions. A Report of Two Cases
Authors: Talpos-Niculescu Roxana M. , Popa Malina , Rusu Laura C. , Pricop Marius O. , Nica Luminita M. , Talpos-Niculescu Serban
Published: May 2021

Background and Objectives: Periapical cystic lesions are a pathology frequently addressed to endodontic specialists. Although their therapy is still not standardized, the treatment should be as conservative as possible and by endodontic means, as they are lesions of endodontic origin. The present case report describes two cases of upper central incisors with large cyst-like periapical lesions, and their one-year follow up. Materials and Methods: Endodontic orthograde treatment was performed under copious irrigation with sodium hypochlorite, in association with calcium hydroxide as an intra-canal medication for both teeth. Root canal filling was achieved in a separate appointment using the continuous wave of condensation technique. A decompression procedure was used in association with endodontic therapy in the second case to reduce the pressure inside the cystic lesion and to allow its drainage, and only because the root canal could not be dried three weeks after medication. Initial cone beam computed tomography (CBCT) investigations, as well as at the one-year follow up, were used to compare the evolution of the lesion. Results: Both cases had a favorable outcome. New bone formation in the periapical region and complete resolution of the lesion was observed at the one-year control in the first case. In the second case, although the lesion was still not completely healed at 12 months, a significant reduction in its size could be observed, showing active signs of healing. Conclusions: Endodontic treatment is the first choice option in the management of teeth with pulpal necrosis and large periapical cystic-like lesions. Decompression is the only surgical procedure recommended when the canals cannot be dried and obturated. Large surgical interventions are unnecessary in cases where endodontic treatment can be performed.
Circulating Metabolites Associated with Body Fat and Lean Mass in Adults with Overweight/Obesity
Authors: Papandreou Christopher , García-Gavilán Jesús , Camacho-Barcia Lucía , Hansen Thea T. , Sjödin Anders , Harrold Joanne A. , Halford Jason C. G. , Bulló Mònica
Published: May 2021

The interplay between fat mass and lean mass within human metabolism is not completely understood. We aimed to identify specific circulating metabolomic profiles associated with these body composition compartments. Cross-sectional analyses were conducted over 236 adults with overweight/obesity from the Satiety Innovation (SATIN) study. Body composition was assessed by dual-energy X-ray absorptiometry. A targeted multiplatform metabolite profiling approach was applied. Associations between 168 circulating metabolites and the body composition measures were assessed using elastic net regression analyses. The accuracy of the multimetabolite weighted models was evaluated using a 10-fold cross-validation approach and the Pearson’s correlation coefficients between metabolomic profiles and body compartments were estimated. Two different profiles including 86 and 65 metabolites were selected for % body fat and lean mass. These metabolites mainly consisted of lipids (sphingomyelins, phosphatidylcholines, lysophosphatidylcholines), acylcarnitines, and amino acids. Several metabolites overlapped between these body composition measures but none of them towards the same direction. The Pearson correlation coefficients between the metabolomic profiles and % body fat or lean mass were 0.80 and 0.79, respectively. Our findings suggest alterations in lipid metabolism, fatty acid oxidation, and protein degradation with increased adiposity and decreased lean body mass. These findings could help us to better understand the interplay between body composition compartments with human metabolic processes.
Iron in Translation: From the Beginning to the End
Authors: Romero Antonia María , Martínez-Pastor María Teresa , Puig Sergi
Published: May 2021

Iron is an essential element for all eukaryotes, since it acts as a cofactor for many enzymes involved in basic cellular functions, including translation. While the mammalian iron-regulatory protein/iron-responsive element (IRP/IRE) system arose as one of the first examples of translational regulation in higher eukaryotes, little is known about the contribution of iron itself to the different stages of eukaryotic translation. In the yeast Saccharomyces cerevisiae, iron deficiency provokes a global impairment of translation at the initiation step, which is mediated by the Gcn2-eIF2α pathway, while the post-transcriptional regulator Cth2 specifically represses the translation of a subgroup of iron-related transcripts. In addition, several steps of the translation process depend on iron-containing enzymes, including particular modifications of translation elongation factors and transfer RNAs (tRNAs), and translation termination by the ATP-binding cassette family member Rli1 (ABCE1 in humans) and the prolyl hydroxylase Tpa1. The influence of these modifications and their correlation with codon bias in the dynamic control of protein biosynthesis, mainly in response to stress, is emerging as an interesting focus of research. Taking S. cerevisiae as a model, we hereby discuss the relevance of iron in the control of global and specific translation steps.
Listeria monocytogenes Cold Shock Proteins: Small Proteins with A Huge Impact
Authors: Muchaamba Francis , Stephan Roger , Tasara Taurai
Published: May 2021

Listeria monocytogenes has evolved an extensive array of mechanisms for coping with stress and adapting to changing environmental conditions, ensuring its virulence phenotype expression. For this reason, L. monocytogenes has been identified as a significant food safety and public health concern. Among these adaptation systems are cold shock proteins (Csps), which facilitate rapid response to stress exposure. L. monocytogenes has three highly conserved csp genes, namely, cspA, cspB, and cspD. Using a series of csp deletion mutants, it has been shown that L. monocytogenes Csps are important for biofilm formation, motility, cold, osmotic, desiccation, and oxidative stress tolerance. Moreover, they are involved in overall virulence by impacting the expression of virulence-associated phenotypes, such as hemolysis and cell invasion. It is postulated that during stress exposure, Csps function to counteract harmful effects of stress, thereby preserving cell functions, such as DNA replication, transcription and translation, ensuring survival and growth of the cell. Interestingly, it seems that Csps might suppress tolerance to some stresses as their removal resulted in increased tolerance to stresses, such as desiccation for some strains. Differences in csp roles among strains from different genetic backgrounds are apparent for desiccation tolerance and biofilm production. Additionally, hierarchical trends for the different Csps and functional redundancies were observed on their influences on stress tolerance and virulence. Overall current data suggest that Csps have a wider role in bacteria physiology than previously assumed.
Antioxidant and Anti-Inflammatory Properties of Probiotic Candidate Strains Isolated during Fermentation of Agave (Agave angustifolia Haw)
Authors: Hernández-Delgado Natalia C. , Torres-Maravilla Edgar , Mayorga-Reyes Lino , Martín Rebeca , Langella Philippe , Pérez-Pastén-Borja Ricardo , Sánchez-Pardo María E. , Bermúdez-Humarán Luis G.
Published: May 2021

Agave species are a source of diverse products for human use, such as food, fiber, and beverages, which include mezcal, a distilled beverage produced by spontaneous fermentation. Agave is an excellent source of high amounts of sugars, minerals, and phenolic compounds, which favor the growth of lactic acid bacteria (LAB) and yeast communities. In this work, 20 promising LAB strains with probiotic characteristics were isolated from the agave fermentation stage in mezcal production. The strains belonged to Lactobacillus plantarum (15), Lactobacillus rhamnosus (2), Enterococcus faecium (2), and Lactococcus lactis (1). These isolates were characterized for their resistance under gastrointestinal conditions, such as lysozyme, acid pH, and bile salts. In addition, the adherence of these LABs to human intestinal epithelial cells (Caco-2 and HT-29 cells) was tested in vitro and their antioxidant and immunomodulatory profile was determined using cellular models. Lactobacillus rhamnosus LM07 and Lactobacillus plantarum LM17 and LM19 strains were selected for their antioxidant properties, and their capacities in an oxidative stress model in intestinal epithelial cells IECs (Caco-2 and HT-29 cells) in the presence of hydrogen peroxide were evaluated. Interestingly, Lactobacillus rhamnosus LM07 and Lactobacillus plantarum LM17 and LM19 strains showed anti-inflammatory properties in TNF-α-stimulated HT-29 cells. Subsequently, bacterial strains exhibiting antioxidant and anti-inflammatory properties were tested in vivo in a mouse model with dinitrobenzene sulfonic acid (DNBS)-induced chronic colitis. Weight loss, intestinal permeability, and cytokine profiles were measured in mice as indicators of inflammation. One of the selected strains, Lactobacillus plantarum LM17, improved the health of the mice, as observed by reduced weight loss, and significantly decreased intestinal permeability. Altogether, our results demonstrate the potential of LAB (and lactobacilli in particular) isolated from the agave fermentation stage in mezcal production. Lactobacillus rhamnosus LM07 and Lactobacillus plantarum LM17 strains represent potential candidates for developing new probiotic supplements to treat inflammatory bowel disease (IBD).
Using Calcined Marls as Non-Common Supplementary Cementitious Materials—A Critical Review
Authors: Bahhou Abdelmoujib , Taha Yassine , Khessaimi Yassine El , Hakkou Rachid , Tagnit-Hamou Arezki , Benzaazoua Mostafa
Published: May 2021

This review summarizes the major research and scientific findings on the relevance of using calcined marl as supplementary cementitious material in developing eco-friendly cement for the next generation. Incorporation of calcined marl into cement can result in changes in the properties of these binders, and thus compatibility with other additions could be potential challenging, particularly at higher replacement ratios. From the reviewed literature, a detailed investigation on the characterization of calcined marls, activation methods, influencing parameters, along with studies on the hydration and microstructure was discussed, the overall objective aimed at coming up with the optimal physical and chemical parameters to generate highly reactive marl.
Use of Natural Clinoptilolite in the Preparation of an Efficient Adsorbent for Ciprofloxacin Removal from Aqueous Media
Authors: Kalebić Barbara , Pavlović Jelena , Dikić Jelena , Rečnik Aleksander , Gyergyek Sašo , Škoro Nikola , Rajić Nevenka
Published: May 2021

The adsorption of the antibiotic ciprofloxacin (CIP) from an aqueous solution by natural zeolite, the calcium-rich clinoptilolite (CLI), and magnetite-coated CLI (MAG-CLI) was investigated. Both CLI and MAG-CLI showed a high adsorption affinity towards CIP at 283, 288 and 293 K at a pH of 5. Adsorption kinetics studied for the initial concentrations of 15–75 mg CIP dm−3 follow Lagergren’s pseudo-second order equation and the adsorption is best represented by the Langmuir model. The adsorption mechanism involves strong electrostatic interactions between negatively charged aluminosilicate lattice and the cationic form of CIP accompanied by an ion-exchange reaction. Magnetite coverage (approx. 12 wt.%) induces magnetism, which can facilitate the separation process. The coverage does not influence the adsorption activity of CLI. The leaching test showed that the MAG coating protects the adsorbent from CIP leaching. This is ascribed to interactions between the CIP carboxyl groups and magnetite nano-particles. Antibacterial tests showed strong antibacterial activity of the ciprofloxacin-containing adsorbents towards pathogenic E. coli and S. aureus.
Intramolecular Photo-Oxidation as a Potential Source to Probe Biological Electron Damage: A Carboxylated Adenosine Analogue as Case Study
Authors: Castellani Maria Elena , Verlet Jan R. R.
Published: May 2021

A carboxylated adenosine analog (C-Ado−) has been synthesized and probed via time-resolved photoelectron spectroscopy in order to induce intra-molecular charge transfer from the carboxylic acid moiety to the nucleobase. Intra-molecular charge transfer can be exploited as starting point to probe low-energy electron (LEE) damage in DNA and its derivatives. Time-dependent density functional theory (TD-DFT) calculations at the B3LYP-6311G level of theory have been performed to verify that the highest occupied molecular orbital (HOMO) was located on carboxylic acid and that the lowest occupied molecular orbital (LUMO) was on the nucleobase. Hence, the carboxylic acid could work as electron source, whilst the nucleobase could serve the purpose of electron acceptor. The dynamics following excitation at 4.66 eV (266 nm) were probed using time-resolved photoelectron spectroscopy using probes at 1.55 eV (800 nm) and 3.10 eV (400 nm). The data show rapid decay of the excited state population and, based on the similarity of the overall dynamics to deoxy-adenosine monophosphate (dAMP–), it appears that the dominant decay mechanism is internal conversion following 1ππ* excitation of the nucleobase, rather than charge-transfer from the carboxylic acid to the nucleobase.
Structural Studies Providing Insights into Production and Conformational Behavior of Amyloid-β Peptide Associated with Alzheimer’s Disease Development
Authors: Urban Anatoly S. , Pavlov Konstantin V. , Kamynina Anna V. , Okhrimenko Ivan S. , Arseniev Alexander S. , Bocharov Eduard V.
Published: May 2021

Alzheimer’s disease is the most common type of neurodegenerative disease in the world. Genetic evidence strongly suggests that aberrant generation, aggregation, and/or clearance of neurotoxic amyloid-β peptides (Aβ) triggers the disease. Aβ accumulates at the points of contact of neurons in ordered cords and fibrils, forming the so-called senile plaques. Aβ isoforms of different lengths are found in healthy human brains regardless of age and appear to play a role in signaling pathways in the brain and to have neuroprotective properties at low concentrations. In recent years, different substances have been developed targeting Aβ production, aggregation, interaction with other molecules, and clearance, including peptide-based drugs. Aβ is a product of sequential cleavage of the membrane glycoprotein APP (amyloid precursor protein) by β- and γ-secretases. A number of familial mutations causing an early onset of the disease have been identified in the APP, especially in its transmembrane domain. The mutations are reported to influence the production, oligomerization, and conformational behavior of Aβ peptides. This review highlights the results of structural studies of the main proteins involved in Alzheimer’s disease pathogenesis and the molecular mechanisms by which perspective therapeutic substances can affect Aβ production and nucleation.
Sambucus Nigra Extracts–Natural Antioxidants and Antimicrobial Compounds
Authors: Przybylska-Balcerek Anna , Szablewski Tomasz , Szwajkowska-Michałek Lidia , Świerk Dariusz , Cegielska-Radziejewska Renata , Krejpcio Zbigniew , Suchowilska Elżbieta , Tomczyk Łukasz , Stuper-Szablewska Kinga
Published: May 2021

Due to the health-promoting properties of elderberry fruits, which result from their rich chemical composition, this raw material is widely used in herbal medicine and the food industry. The aim of the study was to demonstrate the antibacterial activity of the elderberry fruit extracts. The research showed that the content of phenolic acids and flavonoids in the extracts determined their antibacterial activity. The research showed that the content of phenolic acids and flavonoids in the extracts determined their antibacterial activity. The following phenolic acids were predominant: chlorogenic acid, sinapic acid, and t-cinnamic acid. Their average content was, respectively, 139.09, 72.84, 51.29 mg/g extract. Rutin and quercetin (their average content was 1105.39 and 306.6 mg/g extract, respectively) were the dominant flavonoids. The research showed that the elderberry polyphenol extracts exhibited activity against selected strains of bacteria within the concentration range of 0.5–0.05%. The following bacteria were the most sensitive to the extracts: Micrococcus luteus, Proteus mirabilis, Pseudomonas fragii, and Escherichia coli. Of the compounds under analysis, apigenin, kaempferol and ferulic, protocatechuic, and p-coumarin acids had the greatest influence on the high antibacterial activity of elderberry extracts. The results of the microbiological and chemical analyses of the composition of the extracts were analyzed statistically to indicate the bioactive compounds of the greatest antimicrobial significance.
Theoretical Study on the Photo-Oxidation and Photoreduction of an Azetidine Derivative as a Model of DNA Repair
Authors: Navarrete-Miguel Miriam , Francés-Monerris Antonio , Miranda Miguel A. , Lhiaubet-Vallet Virginie , Roca-Sanjuán Daniel
Published: May 2021

Photocycloreversion plays a central role in the study of the repair of DNA lesions, reverting them into the original pyrimidine nucleobases. Particularly, among the proposed mechanisms for the repair of DNA (6-4) photoproducts by photolyases, it has been suggested that it takes place through an intermediate characterized by a four-membered heterocyclic oxetane or azetidine ring, whose opening requires the reduction of the fused nucleobases. The specific role of this electron transfer step and its impact on the ring opening energetics remain to be understood. These processes are studied herein by means of quantum-chemical calculations on the two azetidine stereoisomers obtained from photocycloaddition between 6-azauracil and cyclohexene. First, we analyze the efficiency of the electron-transfer processes by computing the redox properties of the azetidine isomers as well as those of a series of aromatic photosensitizers acting as photoreductants and photo-oxidants. We find certain stereodifferentiation favoring oxidation of the cis-isomer, in agreement with previous experimental data. Second, we determine the reaction profiles of the ring-opening mechanism of the cationic, neutral, and anionic systems and assess their feasibility based on their energy barrier heights and the stability of the reactants and products. Results show that oxidation largely decreases the ring-opening energy barrier for both stereoisomers, even though the process is forecast as too slow to be competitive. Conversely, one-electron reduction dramatically facilitates the ring opening of the azetidine heterocycle. Considering the overall quantum-chemistry findings, N,N-dimethylaniline is proposed as an efficient photosensitizer to trigger the photoinduced cycloreversion of the DNA lesion model.
A Multimethodological Characterization of Cannabis sativa L. Inflorescences from Seven Dioecious Cultivars Grown in Italy: The Effect of Different Harvesting Stages
Authors: Spano Mattia , Di Matteo Giacomo , Ingallina Cinzia , Botta Bruno , Quaglio Deborah , Ghirga Francesca , Balducci Silvia , Cammarone Silvia , Campiglia Enio , Giusti Anna Maria , Vinci Giuliana , Rapa Mattia , Ciano Salvatore , Mannina Luisa , Sobolev Anatoly P.
Published: May 2021

The chemical profile of the female inflorescence extracts from seven Cannabis sativa L. dioecious cultivars (Carmagnola, Fibranova, Eletta Campana, Antal, Tiborszallasi, Kompolti, and Tisza) was monitored at three harvesting stages (4, 14, and 30 September), reaching from the beginning of flowering to end of flowering/beginning of seed formation, using untargeted nuclear magnetic resonance (NMR) and targeted (ultra-high-performance liquid chromatography (UHPLC) and spectrophotometry) analyses. The tetrahydrocannabinol content was always below the legal limits (<0.6%) in all the analyzed samples. The NMR metabolite profile (sugars, organic acids, amino acids, and minor compounds) subjected to principal components analysis (PCA) showed a strong variability according to the harvesting stages: samples harvested in stage I were characterized by a high content of sucrose and myo-inositol, whereas the ones harvested in stage II showed high levels of succinic acid, alanine, valine, isoleucine, phenylalanine, and threonine. Samples harvested in stage III were characterized by high levels of glucose, fructose, choline, trigonelline, malic acid, formic acid, and some amino acids. The ratio between chlorophylls and carotenoids content indicated that all plants grew up exposed to the sun, the Eletta Campana cultivar having the highest pigment amount. Tiborszallasi cultivar showed the highest polyphenol content. The highest antioxidant activity was generally observed in stage II. All these results suggested that the Cannabis sativa L. inflorescences of each analyzed dioecious hemp cultivar presented a peculiar chemical profile affected by the harvesting stage. This information could be useful for producers and industries to harvest inflorescences in the appropriate stage to obtain samples with a peculiar chemical profile suitable for proper applications.
Targeting Multiple Signal Transduction Pathways of SARS-CoV-2: Approaches to COVID-19 Therapeutic Candidates
Authors: Fakhri Sajad , Nouri Zeinab , Moradi Seyed Zachariah , Akkol Esra Küpeli , Piri Sana , Sobarzo-Sánchez Eduardo , Farzaei Mohammad Hosein , Echeverría Javier
Published: May 2021

Due to the complicated pathogenic pathways of coronavirus disease 2019 (COVID-19), related medicinal therapies have remained a clinical challenge. COVID-19 highlights the urgent need to develop mechanistic pathogenic pathways and effective agents for preventing/treating future epidemics. As a result, the destructive pathways of COVID-19 are in the line with clinical symptoms induced by severe acute coronary syndrome (SARS), including lung failure and pneumonia. Accordingly, revealing the exact signaling pathways, including inflammation, oxidative stress, apoptosis, and autophagy, as well as relative representative mediators such as tumor necrosis factor-α (TNF-α), nuclear factor erythroid 2-related factor 2 (Nrf2), Bax/caspases, and Beclin/LC3, respectively, will pave the road for combating COVID-19. Prevailing host factors and multiple steps of SARS-CoV-2 attachment/entry, replication, and assembly/release would be hopeful strategies against COVID-19. This is a comprehensive review of the destructive signaling pathways and host–pathogen interaction of SARS-CoV-2, as well as related therapeutic targets and treatment strategies, including potential natural products-based candidates.
Optimization of the Biosynthesis of B-Ring Ortho-Hydroxy Lated Flavonoids Using the 4-Hydroxyphenylacetate 3-Hydroxylase Complex (HpaBC) of Escherichia coli
Authors: Wang Longji , Ma Xiubing , Ruan Haixiang , Chen Yang , Gao Liping , Lei Ting , Li Yan , Gui Lin , Guo Lina , Xia Tao , Wang Yunsheng
Published: May 2021

Flavonoids are important plant metabolites that exhibit a wide range of physiological and pharmaceutical functions. Because of their wide biological activities, such as anti-inflammatory, antioxidant, antiaging and anticancer, they have been widely used in foods, nutraceutical and pharmaceuticals industries. Here, the hydroxylase complex HpaBC was selected for the efficient in vivo production of ortho-hydroxylated flavonoids. Several HpaBC expression vectors were constructed, and the corresponding products were successfully detected by feeding naringenin to vector-carrying strains. However, when HpaC was linked with an S-Tag on the C terminus, the enzyme activity was significantly affected. The optimal culture conditions were determined, including a substrate concentration of 80 mg·L−1, an induction temperature of 28 °C, an M9 medium, and a substrate delay time of 6 h after IPTG induction. Finally, the efficiency of eriodictyol conversion from P2&3-carrying strains fed naringin was up to 57.67 ± 3.36%. The same strategy was used to produce catechin and caffeic acid, and the highest conversion efficiencies were 35.2 ± 3.14 and 32.93 ± 2.01%, respectively. In this paper, the catalytic activity of HpaBC on dihydrokaempferol and kaempferol was demonstrated for the first time. This study demonstrates a feasible method for efficiently synthesizing in vivo B-ring dihydroxylated flavonoids, such as catechins, flavanols, dihydroflavonols and flavonols, in a bacterial expression system.
Ageratum conyzoides L. and Its Secondary Metabolites in the Management of Different Fungal Pathogens
Authors: Chahal Rubal , Nanda Arun , Akkol Esra Küpeli , Sobarzo-Sánchez Eduardo , Arya Ashwani , Kaushik Deepak , Dutt Rohit , Bhardwaj Rashmi , Rahman Md. Habibur , Mittal Vineet
Published: May 2021

Ageratum conyzoides L. (Family—Asteraceae) is an annual aromatic invasive herb, mainly distributed over the tropical and subtropical regions of the world. It owns a reputed history of indigenous remedial uses, including as a wound dressing, an antimicrobial, and mouthwash as well as in treatment of dysentery, diarrhea, skin diseases, etc. In this review, the core idea is to present the antifungal potential of the selected medicinal plant and its secondary metabolites against different fungal pathogens. Additionally, toxicological studies (safety profile) conducted on the amazing plant A. conyzoides L. are discussed for the possible clinical development of this medicinal herb. Articles available from 2000 to 2020 were reviewed in detail to exhibit recent appraisals of the antifungal properties of A. conyzoides. Efforts were aimed at delivering evidences for the medicinal application of A. conyzoides by using globally recognized scientific search engines and databases so that an efficient approach for filling the lacunae in the research and development of antifungal drugs can be adopted. After analyzing the literature, it can be reported that the selected medicinal plant effectively suppressed the growth of numerous fungal species, such as Aspergillus, Alternaria, Candida, Fusarium, Phytophthora, and Pythium, owing to the presence of various secondary metabolites, particularly chromenes, terpenoids, flavonoids and coumarins. The possible mechanism of action of different secondary metabolites of the plant against fungal pathogens is also discussed briefly. However, it was found that only a few studies have been performed to demonstrate the plant’s dosage and safety profile in humans. Considered all together, A. conyzoides extract and its constituents may act as a promising biosource for the development of effective antifungal formulations for clinical use. However, in order to establish safety and efficacy, additional scientific research is required to explore chronic toxicological effects of ageratum, to determine the probability of interactions when used with different herbs, and to identify safe dosage. The particulars presented here not only bridge this gap but also furnish future research strategies for the investigators in microbiology, ethno-pharmacology, and drug discovery.
Secreted Enzyme-Responsive System for Controlled Antifungal Agent Release
Authors: Bernardos Andrea , Božik Matěj , Montero Ana , Pérez-Esteve Édgar , García-Casado Esther , Lhotka Miloslav , Fraňková Adéla , Marcos María Dolores , Barat José Manuel , Martínez-Máñez Ramón , Klouček Pavel
Published: May 2021

Essential oil components (EOCs) such as eugenol play a significant role in plant antimicrobial defense. Due to the volatility and general reactivity of these molecules, plants have evolved smart systems for their storage and release, which are key prerequisites for their efficient use. In this study, biomimetic systems for the controlled release of eugenol, inspired by natural plant defense mechanisms, were prepared and their antifungal activity is described. Delivery and antifungal studies of mesoporous silica nanoparticles (MSN) loaded with eugenol and capped with different saccharide gates—starch, maltodextrin, maltose and glucose—against fungus Aspergillus niger—were performed. The maltodextrin- and maltose-capped systems show very low eugenol release in the absence of the fungus Aspergillus niger but high cargo delivery in its presence. The anchored saccharides are degraded by exogenous enzymes, resulting in eugenol release and efficient inhibition of fungal growth.
L-Cysteine as an Irreversible Inhibitor of the Peroxidase-Mimic Catalytic Activity of 2-Dimensional Ni-Based Nanozymes
Authors: Liyanage Piyumi , Weerathunge Pabudi , Singh Mandeep , Bansal Vipul , Ramanathan Rajesh
Published: May 2021

The ability to modulate the catalytic activity of inorganic nanozymes is of high interest. In particular, understanding the interactions of inhibitor molecules with nanozymes can bring them one step closer to the natural enzymes and has thus started to attract intense interest. To date, a few reversible inhibitors of the nanozyme activity have been reported. However, there are no reports of irreversible inhibitor molecules that can permanently inhibit the activity of nanozymes. In the current work, we show the ability of L-cysteine to act as an irreversible inhibitor to permanently block the nanozyme activity of 2-dimensional (2D) NiO nanosheets. Determination of the steady state kinetic parameters allowed us to obtain mechanistic insights into the catalytic inhibition process. Further, based on the irreversible catalytic inhibition capability of L-cysteine, we demonstrate a highly specific sensor for the detection of this biologically important molecule.
Iron Beats Electricity: Resistance Training but Not Whole-Body Electromyostimulation Improves Cardiometabolic Health in Obese Metabolic Syndrome Patients during Caloric Restriction—A Randomized-Controlled Study
Authors: Reljic Dejan , Herrmann Hans J. , Neurath Markus F. , Zopf Yurdagül
Published: May 2021

Caloric restriction (CR) and exercise are cornerstones in the treatment of obesity and cardiometabolic disorders. Recently, whole body electromyostimulation (WB-EMS) has emerged as a more time-efficient alternative to traditional resistance training (RT). However, the effects of WB-EMS compared to RT on cardiometabolic health in obese metabolic syndrome (MetS) patients performed during CR are still unclear. In total, 118 obese MetS patients (52.7 ± 11.8 years, BMI: 38.1 ± 6.9 kg/m2) undergoing CR over 12 weeks (aim: −500 kcal deficit/day) were randomly allocated to either WB-EMS, single-set RT (1-RT), 3-set RT (3-RT) or an inactive control group (CON). Primary outcome was MetS severity (MetS z-score). Secondary outcomes were body composition, muscle strength and quality of life (QoL). All groups significantly reduced body weight (~3%) and fat mass (~2.6 kg) but only 1-RT and 3-RT preserved skeletal muscle mass (SMM). All exercise groups increased muscle strength in major muscle groups (20–103%). However, only the two RT-groups improved MetS z-score (1-RT: −1.34, p = 0.003; 3-RT: −2.06, p < 0.001) and QoL (1-RT: +6%, p = 0.027; 3-RT: +12%, p < 0.001), while WB-EMS and CON had no impact on these outcomes. We conclude that traditional RT has superior effects on cardiometabolic health, SMM and QoL in obese MetS patients undergoing CR than WB-EMS.
Teacher Evaluation of an Experiential Vegetable Education Program for Australian Primary Schools: Does Face-to-Face Training Add Value above Digital Training?
Authors: Poelman Astrid A. M. , Cochet-Broch Maeva , Beelen Janne , Wiggins Bonnie , Heffernan Jessica E. , Cox David N.
Published: May 2021

The teacher-led implementation of healthy eating programs in schools is cost-effective and potentially impactful. Teacher acceptability is important for uptake; however, process evaluations are scarce. This study evaluated the effect of two intensities of teacher training on the evaluation of a vegetable education program for Australian primary schools by teachers. The teachers (n = 65) who implemented the program as part of a cluster RCT (25 schools in two states, New South Wales and South Australia) received either low- (provision with materials and online training) or high (additional face-to-face (F2F) training)-intensity training prior to implementing a 5-week vegetable education program. They evaluated the acceptability of a digital training module and program by indicating the level of agreement with 15 and 18 statements, respectively, using 5-point Likert scales. The average item scores ranged from 3.0 to 4.2. All but one item, including student engagement, alignment to the curriculum and intent for reuse of the program, had a rounded average or median score of 4. The level of training intensity did not impact the teacher acceptability ratings. In conclusion, the teacher acceptability was good, and additional F2F training does not add value above the solely digital training of the teachers.
Eating Motives and Other Factors Predicting Emotional Overeating during COVID-19 in a Sample of Polish Adults
Authors: Modrzejewska Adriana , Czepczor-Bernat Kamila , Modrzejewska Justyna , Matusik Paweł
Published: May 2021

We hypothesised that the higher levels of emotion-related predictors (eating motive in the form of affect regulation and COVID-19-related stress) would be associated with higher emotional overeating, after accounting for the effects of demographic variables (gender and BMI) and other eating motives (visual- and attitude-related predictors: liking, pleasure, visual appeal; body- and health-related predictors: need and hunger, health, weight control). Participants (N = 868; Mage = 33.53 years, SD = 11.98) completed: the Eating Motivation Survey, the Emotional Overeating Questionnaire, a COVID-19-related stress measure and a socio-demographic survey. The final step of the regression with emotional overeating was significant; affect regulation and COVID-19-related stress were significantly related to emotional overeating (ΔF p < 0.001, Adj. ΔR2 = 0.13). During the COVID-19 pandemic, eating can, on the one hand, help to cope with the current difficult situation and the negative emotions associated with it; on the other hand, frequent use of this tendency can lead to rigid regulation of affect and use of this mechanism as the dominant mechanism. Therefore, limited social contact, related disruptions in daily activities and stress resulting from COVID-19 should generate appropriate interventions, not necessarily focusing only on emotional eating, but also on the resources of the individual. It is worth encouraging specialists to implement alternative methods of contact with their patients, e.g., online.