bluuebunny/crossref_metadata_2025 huggingface dataset:
Gallstone Disease and Microbiome
Authors: Grigor’eva Irina N. , Romanova Tatyana I.
Published: June 2020

Gallstone disease (GSD) has, for many years, remained a high-cost, socially significant public health problem. Over the past decade, a number of studies have been carried out—both in humans and in animal models—confirming the role of the microbiota in various sections of the gastrointestinal tract as a new link in the etiopathogenesis of GSD. The microbiome of bile correlates with the bacterial composition of saliva, and the microbiome of the biliary tract has a high similarity with the microbiota of the duodenum. Pathogenic microflora of the oral cavity, through mechanisms of immunomodulation, can affect the motility of the gallbladder and the expression of mucin genes (MUC1, Muc3, MUC4), and represent one of the promoters of stone formation in the gallbladder. The presence of H. pylori infection contributes to the formation of gallstones and affects the occurrence of complications of GSD, including acute and chronic cholecystitis, cholangitis, pancreatitis. Intestinal bacteria (Clostridium, Bifidobacterium, Peptostreptococcus, Bacteroides, Eubacterium, and Escherichia coli) participating in the oxidation and epimerization of bile acids can disrupt enterohepatic circulation and lead to the formation of gallstones. At the same time, cholecystectomy due to GSD leads to the further transformation of the composition of the microbiota in various parts of the gastrointestinal tract, increasing the risk of developing stomach cancer and colorectal cancer. Further research is required to determine the possibility of using the evaluation of the composition of the microbiota of the gastrointestinal and biliary tracts as an early diagnostic marker of various gastroenterological diseases.
Synthesis, Characterization and Biological Evaluation of Metal Adamantyl 2-Pyridylhydrazone Complexes
Authors: Shehadi Ihsan A. , Delmani Fatima-Azzahra , Jaber Areej M. , Hammad Hana , AlDamen Murad A. , Al-Qawasmeh Raed A. , Khanfar Monther A.
Published: June 2020

Four new complexes derived from adamantly containing hydrazone (APH) ligand with Cu(II) (1), Co(II) (2), Ni(II) (3) and Zn(II) (4), have been synthesized and characterized using different physicochemical methods. The structure of the ligand APH and its copper complex 1 have been established by single-crystal X-ray diffraction direct methods, which reveal that complex 1 has distorted square-pyramidal geometry. Complexes 1–4 are screened against seven human cancer cell lines namely, breast cancer cell lines (MCF7, T47D, MDA-MB-231), prostate cancer cell lines (PC3, DU145) and the colorectal cancer cell line Coco-2, for their antiproliferative activities. Complex 1 has shown a promising anticancer activity compared to the other ones. The structural and spectroscopic analysis of APH and its complexes are confirmed by DFT calculations.
Delivery of Alpha-Mangostin Using Cyclodextrins through a Biological Membrane: Molecular Dynamics Simulation
Authors: Hotarat Wiparat , Nutho Bodee , Wolschann Peter , Rungrotmongkol Thanyada , Hannongbua Supot
Published: June 2020

α-Mangostin (MGS) exhibits various pharmacological activities, including antioxidant, anticancer, antibacterial, and anti-inflammatory properties. However, its low water solubility is the major obstacle for its use in pharmaceutical applications. To increase the water solubility of MGS, complex formation with beta-cyclodextrins (βCDs), particularly with the native βCD and/or its derivative 2,6-dimethyl-β-CD (DMβCD) is a promising technique. Although there have been several reports on the adsorption of βCDs on the lipid bilayer, the release of the MGS/βCDs inclusion complex through the biological membrane remains unclear. In this present study, the release the MGS from the two different βCDs (βCD and DMβCD) across the lipid bilayer was investigated. Firstly, the adsorption of the free MGS, free βCDs, and inclusion complex formation was studied by conventional molecular dynamics simulation. The MGS in complex with those two βCDs was able to spontaneously release free MGS into the inner membrane. However, both MGS and DMβCD molecules potentially permeated into the deeper region of the interior membrane, whereas βCD only adsorbed at the outer membrane surface. The interaction between secondary rim of βCD and the 1-palmitoeyl-2-oleoyl-glycero-3-phosphocholine (POPC) phosphate groups showed the highest number of hydrogen bonds (up to 14) corresponding to the favorable location of βCD on the POPC membrane. Additionally, the findings suggested that electrostatic energy was the main driving force for βCD adsorption on the POPC membrane, while van der Waals interactions played a predominant role in DMβCD adsorption. The release profile of MGS from the βCDs pocket across the lipid bilayer exhibited two energy minima along the reaction coordinate associated with the permeation of the MGS molecule into the deeper region of the POPC membrane.
Nitrosative Stress and Its Association with Cardiometabolic Disorders
Authors: Pérez-Torres Israel , Manzano-Pech Linaloe , Rubio-Ruíz María Esther , Soto María Elena , Guarner-Lans Verónica
Published: June 2020

Reactive nitrogen species (RNS) are formed when there is an abnormal increase in the level of nitric oxide (NO) produced by the inducible nitric oxide synthase (iNOS) and/or by the uncoupled endothelial nitric oxide synthase (eNOS). The presence of high concentrations of superoxide anions (O2−) is also necessary for their formation. RNS react three times faster than O2− with other molecules and have a longer mean half life. They cause irreversible damage to cell membranes, proteins, mitochondria, the endoplasmic reticulum, nucleic acids and enzymes, altering their activity and leading to necrosis and to cell death. Although nitrogen species are important in the redox imbalance, this review focuses on the alterations caused by the RNS in the cellular redox system that are associated with cardiometabolic diseases. Currently, nitrosative stress (NSS) is implied in the pathogenesis of many diseases. The mechanisms that produce damage remain poorly understood. In this paper, we summarize the current knowledge on the participation of NSS in the pathology of cardiometabolic diseases and their possible mechanisms of action. This information might be useful for the future proposal of anti-NSS therapies for cardiometabolic diseases.
Determination and Identification of Antibiotic Drugs and Bacterial Strains in Biological Samples
Authors: Pauter Katarzyna , Szultka-Młyńska Małgorzata , Buszewski Bogusław
Published: June 2020

Antibiotics were initially natural substances. However, nowadays, they also include synthetic drugs, which show their activity against bacteria, killing or inhibiting their growth and division. Thanks to these properties, many antibiotics have quickly found practical application in the fight against infectious diseases such as tuberculosis, syphilis, gastrointestinal infections, pneumonia, bronchitis, meningitis and septicemia. Antibiotic resistance is currently a detrimental problem; therefore, in addition to the improvement of antibiotic therapy, attention should also be paid to active metabolites in the body, which may play an important role in exacerbating the existing problem. Taking into account the clinical, cognitive and diagnostic purposes of drug monitoring, it is important to select an appropriate analytical method that meets all the requirements. The detection and identification of the microorganism responsible for the infection is also an essential factor in the implementation of appropriate antibiotic therapy. In recent years, clinical microbiology laboratories have experienced revolutionary changes in the way microorganisms are identified. The MALDI-TOF MS technique may be interesting, especially in some areas where a quick analysis is required, as is the case with clinical microbiology. This method is not targeted, which means that no prior knowledge of the infectious agent is required, since identification is based on a database match.
Combretastatins: An Overview of Structure, Probable Mechanisms of Action and Potential Applications
Authors: Karatoprak Gökçe Şeker , Küpeli Akkol Esra , Genç Yasin , Bardakcı Hilal , Yücel Çiğdem , Sobarzo-Sánchez Eduardo
Published: June 2020

Combretastatins are a class of closely related stilbenes (combretastatins A), dihydrostilbenes (combretastatins B), phenanthrenes (combretastatins C) and macrocyclic lactones (combretastatins D) found in the bark of Combretum caffrum (Eckl. & Zeyh.) Kuntze, commonly known as the South African bush willow. Some of the compounds in this series have been shown to be among the most potent antitubulin agents known. Due to their structural simplicity many analogs have also been synthesized. Combretastatin A4 phosphate is the most frequently tested compounds in preclinical and clinical trials. It is a water-soluble prodrug that the body can rapidly metabolize to combretastatin A4, which exhibits anti-tumor properties. In addition, in vitro and in vivo studies on combretastatins have determined that these compounds also have antioxidant, anti-inflammatory and antimicrobial effects. Nano-based formulations of natural or synthetic active agents such as combretastatin A4 phosphate exhibit several clear advantages, including improved low water solubility, prolonged circulation, drug targeting properties, enhanced efficiency, as well as fewer side effects. In this review, a synopsis of the recent literature exploring the combretastatins, their potential effects and nanoformulations as lead compounds in clinical applications is provided.
Effects of Thermal Treatment on Natural Clinoptilolite-Rich Zeolite Behavior in Simulated Biological Fluids
Authors: Cadar Oana , Senila Marin , Hoaghia Maria-Alexandra , Scurtu Daniela , Miu Ion , Levei Erika Andrea
Published: June 2020

This study presents the effect of thermal treatment (450, 500, 600, 750, and 800 °C) on a Romanian clinoptilolite-rich natural zeolite, along with the interaction of raw and thermally treated zeolites with simulated gastric fluid (SGF, pH = 1.20) at different zeolite to SGF ratios and exposure times. The zeolites were characterized using gravimetric analysis, X-ray fluorescence, powder X-ray diffraction (pXRD), and Fourier transform infrared (FT-IR) spectroscopy. The chemical composition of the zeolite subjected to thermal treatment did not change significantly with the increase of temperature. Structural changes were not detectable by pXRD and FT-IR analyses in the zeolites thermally treated up to 500 °C, while above 600 °C a gradual structural breakdown of zeolite was noticed. At high temperatures, the broad, low-intensity peaks in pXRD patterns indicated the partial amorphization of the crystalline structure. The pXRD and FT-IR analyses showed that the crystalline structure of zeolites remains unaffected after their exposure to SGF. The results revealed that the amounts of Fe, Na, Mg, K, Ca, Al, and Si released depends mainly on the zeolite to SGF ratio, and to a lower extent on the thermal treatment temperature, while the exposure time of 1 to 7 days does not have a significant impact on the elements released in SGF.
Quercetin Inhibits Lef1 and Resensitizes Docetaxel-Resistant Breast Cancer Cells
Authors: Prieto-Vila Marta , Shimomura Iwao , Kogure Akiko , Usuba Wataru , Takahashi Ryou-u , Ochiya Takahiro , Yamamoto Yusuke
Published: June 2020

Drug resistance is a major problem for breast cancer patients. Docetaxel is an anti-mitotic agent that serves as first line of treatment in metastatic breast cancer, however it is susceptible to cellular drug resistance. Drug-resistant cells are able to spread during treatment, leading to treatment failure and eventually metastasis, which remains the main cause for cancer-associated death. In previous studies, we used single-cell technologies and identified a set of genes that exhibit increased expression in drug-resistant cells, and they are mainly regulated by Lef1. Furthermore, upregulating Lef1 in parental cells caused them to become drug resistant. Therefore, we hypothesized that inhibiting Lef1 could resensitize cells to docetaxel. Here, we confirmed that Lef1 inhibition, especially on treatment with the small molecule quercetin, decreased the expression of Lef1 and resensitized cells to docetaxel. Our results demonstrate that Lef1 inhibition also downregulated ABCG2, Vim, and Cav1 expression and equally decreased Smad-dependent TGF-β signaling pathway activation. Likewise, these two molecules worked in a synergetic manner, greatly reducing the viability of drug-resistant cells. Prior studies in phase I clinical trials have already shown that quercetin can be safely administered to patients. Therefore, the use of quercetin as an adjuvant treatment in addition to docetaxel for the treatment of breast cancer may be a promising therapeutic approach.
Oxyresveratrol Possesses DNA Damaging Activity
Authors: Radapong Sarayut , Sarker Satyajit D. , Ritchie Kenneth J.
Published: June 2020

Artocarpus lakoocha Wall. ex Roxb. (family: Moraceae) has been used as a traditional Thai medicine for the treatment of various parasitic diseases. This species has been reported to be the source of phytochemicals, which show potent biological activities. The objective of this study was to investigate the phytochemical profile of the extracts of the heartwood of A. lakoocha and their pro-oxidant activity in vitro. The heartwood was ground, extracted, and then chromatographic and spectroscopic analyses were carried out; oxyresveratrol was identified as the major component in the extracts. The pro-oxidant activity was investigated using DNA-nick, reactive oxygen species and reducing assays. The results showed that oxyresveratrol induced DNA damage dose-dependently in the presence of copper (II) ions. It was also found to generate reactive oxygen species (ROS) in a dose-dependent manner and reduce copper (II) to copper (I). It is concluded that oxyresveratrol is the most abundant stilbenoid in A. lakoocha heartwood. The compound exhibited pro-oxidant activity in the presence of copper (II) ions, which may be associated with its ability to act as an anticancer compound.
Beer Phenolic Composition of Simple Phenols, Prenylated Flavonoids and Alkylresorcinols
Authors: Boronat Anna , Soldevila-Domenech Natalia , Rodríguez-Morató Jose , Martínez-Huélamo Miriam , Lamuela-Raventós Rosa M. , de la Torre Rafael
Published: June 2020

Beer is a fermented beverage with beneficial phenolic compounds and is widely consumed worldwide. The current study aimed to describe the content of three families of phenolic compounds with relevant biological activities: prenylated flavonoids (from hops), simple phenolic alcohols (from fermentation) and alkylresorcinols (from cereals) in a large sample of beers (n = 45). The prenylated flavonoids analyzed were xanthohumol, isoxanthohumol, 6- and 8-prenylnaringenin. The total prenylated flavonoids present in beer ranged from 0.0 to 9.5 mg/L. The simple phenolic alcohols analyzed were tyrosol and hydroxytyrosol, ranging from 0.2 to 44.4 and 0.0 to 0.1 mg/L, respectively. Our study describes, for the first time, the presence of low amounts of alkylresorcinols in beer, in concentrations ranging from 0.02 to 11.0 µg/L. The results in non-alcoholic beer and the differences observed in the phenolic composition among different beer types and styles highlight the importance of the starting materials and the brewing process (especially fermentation) on the final phenolic composition of beer. In conclusion, beer represents a source of phenolic compounds in the diet that could act synergistically, triggering beneficial health effects in the context of its moderate consumption.
Use of Nanomaterial-Based (Micro)Extraction Techniques for the Determination of Cosmetic-Related Compounds
Authors: Grau José , Benedé Juan L. , Chisvert Alberto
Published: June 2020

The high consumer demand for cosmetic products has caused the authorities and the industry to require rigorous analytical controls to assure their safety and efficacy. Thus, the determination of prohibited compounds that could be present at trace level due to unintended causes is increasingly important. Furthermore, some cosmetic ingredients can be percutaneously absorbed, further metabolized and eventually excreted or bioaccumulated. Either the parent compound and/or their metabolites can cause adverse health effects even at trace level. Moreover, due to the increasing use of cosmetics, some of their ingredients have reached the environment, where they are accumulated causing harmful effects in the flora and fauna at trace levels. To this regard, the development of sensitive analytical methods to determine these cosmetic-related compounds either for cosmetic control, for percutaneous absorption studies or for environmental surveillance monitoring is of high interest. In this sense, (micro)extraction techniques based on nanomaterials as extraction phase have attracted attention during the last years, since they allow to reach the desired selectivity. The aim of this review is to provide a compilation of those nanomaterial-based (micro)extraction techniques for the determination of cosmetic-related compounds in cosmetic, biological and/or environmental samples spanning from the first attempt in 2010 to the present.
Mutagenesis and Adaptation of the Psychrotrophic Fungus Chrysosporium pannorum A-1 as a Method for Improving β-pinene Bioconversion
Authors: Kutyła Mateusz , Fiedurek Jan , Gromada Anna , Jędrzejewski Krzysztof , Trytek Mariusz
Published: June 2020

Mutagenesis and adaptation of the psychrotrophic fungus Chrysosporium pannorum A-1 to the toxic substrate β-pinene were used to obtain a biocatalyst with increased resistance to this terpene and improved bioconversion properties. Mutants of the parental strain were induced with UV light and N-methyl-N′-nitro-N-nitrosoguanidine. Mutants resistant to β-pinene were isolated using agar plates with a linear gradient of substrate concentrations. Active mutants were selected based on their general metabolic activity (GMA) expressed as oxygen consumption rate. Compared to the parental strain, the most active mutant showed an enhanced biotransformation ability to convert β-pinene to trans-pinocarveol (315 mg per g of dry mycelium), a 4.3-fold greater biocatalytic activity, and a higher resistance to H2O2-induced oxidative stress. Biotransformation using adapted mutants yielded twice as much trans-pinocarveol as the reaction catalyzed by non-adapted mutants. The results indicate that mutagenesis and adaptation of C. pannorum A-1 is an effective method of enhancing β-bioconversion of terpenes.
Human Brain Shows Recurrent Non-Canonical MicroRNA Editing Events Enriched for Seed Sequence with Possible Functional Consequence
Authors: Paul Deepanjan , Ansari Asgar Hussain , Lal Megha , Mukhopadhyay Arijit
Published: June 2020

RNA editing is a post-transcriptional modification, which can provide tissue-specific functions not encoded in DNA. Adenosine-to-inosine is the predominant editing event and, along with cytosine-to-uracil changes, constitutes canonical editing. The rest is non-canonical editing. In this study, we have analysed non-canonical editing of microRNAs in the human brain. We have performed massively parallel small RNA sequencing of frontal cortex (FC) and corpus callosum (CC) pairs from nine normal individuals (post-mortem). We found 113 and 90 unique non-canonical editing events in FC and CC samples, respectively. More than 70% of events were in the miRNA seed sequence—implicating an altered set of target mRNAs and possibly resulting in a functional consequence. Up to 15% of these events were recurring and found in at least three samples, also supporting the biological relevance of such variations. Two specific sequence variations, C-to-A and G-to-U, accounted for over 80% of non-canonical miRNA editing events—and revealed preferred sequence motifs. Our study is one of the first reporting non-canonical editing in miRNAs in the human brain. Our results implicate miRNA non-canonical editing as one of the contributing factors towards transcriptomic diversity in the human brain.
Reduction-Responsive Molecularly Imprinted Poly(2-isopropenyl-2-oxazoline) for Controlled Release of Anticancer Agents
Authors: Cegłowski Michał , Jerca Valentin Victor , Jerca Florica Adriana , Hoogenboom Richard
Published: June 2020

Trigger-responsive materials are capable of controlled drug release in the presence of a specific trigger. Reduction induced drug release is especially interesting as the reductive stress is higher inside cells than in the bloodstream, providing a conceptual controlled release mechanism after cellular uptake. In this work, we report the synthesis of 5-fluorouracil (5-FU) molecularly imprinted polymers (MIPs) based on poly(2-isopropenyl-2-oxazoline) (PiPOx) using 3,3′-dithiodipropionic acid (DTDPA) as a reduction-responsive functional cross-linker. The disulfide bond of DTDPA can be cleaved by the addition of tris(2-carboxyethyl)phosphine (TCEP), leading to a reduction-induced 5-FU release. Adsorption isotherms and kinetics for 5-FU indicate that the adsorption kinetics process for imprinted and non-imprinted adsorbents follows two different kinetic models, thus suggesting that different mechanisms are responsible for adsorption. The release kinetics revealed that the addition of TCEP significantly influenced the release of 5-FU from PiPOx-MIP, whereas for non-imprinted PiPOx, no statistically relevant differences were observed. This work provides a conceptual basis for reduction-induced 5-FU release from molecularly imprinted PiPOx, which in future work may be further developed into MIP nanoparticles for the controlled release of therapeutic agents.
Nano-Polyplexes Mediated Transfection of Runx2-shRNA Mitigates the Osteodifferentiation of Human Valvular Interstitial Cells
Authors: Voicu Geanina , Rebleanu Daniela , Constantinescu Cristina Ana , Fuior Elena Valeria , Ciortan Letitia , Droc Ionel , Uritu Cristina Mariana , Pinteala Mariana , Manduteanu Ileana , Simionescu Maya , Calin Manuela
Published: June 2020

Calcific aortic valve disease (CAVD) is a progressive disorder that increases in prevalence with age. An important role in aortic valve calcification is played by valvular interstitial cells (VIC), that with age or in pathological conditions acquire an osteoblast-like phenotype that advances the disease. Therefore, pharmacological interventions aiming to stop or reverse the osteoblastic transition of VIC may represent a therapeutic option for CAVD. In this study, we aimed at developing a nanotherapeutic strategy able to prevent the phenotypic switch of human aortic VIC into osteoblast-like cells. We hypothesize that nanocarriers designed for silencing the Runt-related transcription factor 2 (Runx2) will stop the progress or reverse the osteodifferentiation of human VIC, induced by high glucose concentrations and pro-osteogenic factors. We report here the potential of fullerene (C60)-polyethyleneimine (PEI)/short hairpin (sh)RNA-Runx2 nano-polyplexes to efficiently down-regulate Runx2 mRNA and protein expression leading subsequently to a significant reduction in the expression of osteogenic proteins (i.e., ALP, BSP, OSP and BMP4) in osteoblast-committed VIC. The data suggest that the silencing of Runx2 could represent a novel strategy to impede the osteoblastic phenotypic shift of VIC and the ensuing progress of CAVD.
Comparative Germination Ecology of Two Endemic Rhaponticum Species (Asteraceae) in Different Climatic Zones of the Ligurian and Maritime Alps (Piedmont, Italy)
Authors: Carasso Valentina , Mucciarelli Marco , Dovana Francesco , Müller Jonas V
Published: June 2020

Comparative studies of seed germination of closely related taxa can help increase our understanding of the ecological limitations of cold-adapted plants and forecast how they might respond to global warming. No studies exist on the relationship between thermoclimatic belts that classify mountain life zones according to bioclimatic criteria and the germination strategy of alpine plants. The aim of this study was to assess this relationship using two closely related species growing in different thermotypes and to test whether their germination responses were related to the climate at natural sites. Fresh Rhaponticum bicknellii and R. scariosum seeds were cold stratified for 0, 30, 60 and 90 days and tested for germination at 10, 15 and 20 °C. At the same time, seed burial experiments were run in the field and in the plant nursery. A GLM analysis showed that the length of cold stratification affected significantly only the germination of R. bicknellii seeds, while increasing temperatures prompted germination in both species. We found that R. bicknellii adopts a drought-avoiding germination strategy, while R. scariosum germination is favoured by warm temperatures. Our findings support the general view that alpine plants do not share common germination requirements and that any conclusions should be interpreted from a biogeographical and bioclimatic perspective. Therefore, seed germination and seedling establishment of endemic alpine species can also be predicted by looking at the bioclimate of the species’ range.
Together for the Better: Improvement of a Model Based Strategy for Grapevine Downy Mildew Control by Addition of Potassium Phosphonates
Authors: Bleyer Gottfried , Lösch Fedor , Schumacher Stefan , Fuchs René
Published: June 2020

Grapevine downy mildew is one of the major diseases in viticulture. To control this disease, a more effective strategy has been developed and established based on growth and model data as well as on a combination of fungicides. For this purpose, the systemic plant protection product potassium phosphonate (PP) was combined with two contact fungicides. Treatments were carried out according to the different experimental conditions after the growth of 400 cm2, 600 cm2, and 800 cm2 leaf area per primary shoot. PP increased the effectiveness of the preventive fungicides whenever high infection pressure was the case. The experiments also show that it is possible to extend the treatment intervals from 400 cm2 to 600 cm2 new leaf area when PP was added. However, none of the tested treatments were sufficient for the extension to intervals of 800 cm2. These data show that PP can be a key factor in the reduction of the application of synthetic or copper-based fungicides.
Synthesis and Application of New Amphiphilic Asphaltene Ionic Liquid Polymers to Demulsify Arabic Heavy Petroleum Crude Oil Emulsions
Authors: Ismail Ali I. , Atta Ayman M. , El-Newehy Mohamed , El-Hefnawy Mohamed E.
Published: June 2020

Asphaltenes are heavy petroleum crude oil components which limit the production of petroleum crude oil due to their aggregation and their stabilization for all petroleum crude oil water emulsions. The present study aimed to modify the chemical structures of isolated asphaltenes by converting them into amphiphilic polymers containing ionic liquid moieties (PILs) to demulsify the emulsion and replace the asphaltene layers surrounding the oil or water droplets in petroleum crude oil emulsions. The literature survey indicated that no modification occurred to produce the PILs from the asphaltenes. In this respect, the asphaltenes were modified via oxidation of the lower aliphatic chain through carboxylation followed by conversion to asphaltene acid chloride that reacted with ethoxylated N-alkyl pyridinium derivatives. Moreover, the carboxylation of asphaltenes was carried out through the Diels–Alder reaction with maleic anhydride that was linked with ethoxylated N-alkyl pyridinium derivatives to produce amphiphilic asphaltene PILs. The produced PILs from asphaltenes acid chloride and maleic anhydride were designated as AIL and AIL-2. The chemical structure and thermal stability of the polymeric asphaltene ionic liquids were evaluated. The modified structure of asphaltenes AIL and AIL-2 exhibited different thermal characteristics involving glass transition temperatures (Tg) at −68 °C and −45 °C, respectively. The new asphaltenes ionic liquids were adsorbed at the asphaltenes surfaces to demulsify the heavy petroleum crude emulsions. The demulsification data indicated that the mixing of AIL and AIL-2 100 at different ratios with ethoxylated N-alkyl pyridinium were demulsified with 100% of the water from different compositions of O:W emulsions 50:50, 90:10, and 10:90. The demulsification times for the 50:50, 90:10, and 10:90 O:W emulsions were 120, 120, and 60 min, respectively. The interaction of the PILs with asphaltene and mechanism of demulsification was also investigated.
A Very High-Speed Validation Scheme Based on Template Matching for Segmented Character Expiration Codes on Beverage Cans
Authors: Rodríguez-Rodríguez José C. , de Blasio Gabriele S. , García Carmelo R. , Quesada-Arencibia Alexis
Published: June 2020

This paper expands upon a previous publication and is the natural continuation of an earlier study which presented an industrial validator of expiration codes printed on aluminium or tin cans, called MONICOD. MONICOD is distinguished by its high operating speed, running at 200 frames per second and validating up to 35 cans per second. This paper adds further detail to this description by describing the final stage of the MONICOD industrial validator: the process of effectively validating the characters. In this process we compare the acquired shapes, segmented during the prior stages, with expected character shapes. To do this, we use a template matching scheme (here called “morphologies”) based on bitwise operations. Two learning algorithms for building the valid morphology databases are also presented. The results of the study presented here show that in the acquisition of 9885 frames containing 465 cans to be validated, there was only one false positive (0.21% of the total). Another notable feature is that it is at least 20% faster in validation time with error rates similar to those of classifiers such as support vector machines (SVM), radial base functions (RBF), multi-layer perceptron with backpropagation (MLP) and k-nearest neighbours (KNN).
Modeling Volatility Characteristics of Epileptic EEGs using GARCH Models
Authors: Follis Jack L. , Lai Dejian
Published: June 2020

Objective: To determine if there was a difference in the volatility characteristics of seizure and non-seizure onset channels in the intracranial electroencephalogram (EEG) in a patient with temporal lobe epilepsy. Methods: The half-life of volatility for the different EEG channels was determined using Autoregressive Moving Average–Generalized Autoregressive Conditional Heteroscedasticity (ARMA–GARCH) models; confidence intervals were constructed using the delta method and an asymptotic method for comparing the half-lives. Results: Clinically determined seizure onsets occurred over strip electrodes named RAST (Right Anterior Subtemporal) and RMST (Right Mid Subtemporal), at locations 2, 3 and 4, on the strip electrodes. The half-lives of volatility for two of the three seizure channels, RAST3 and RAST4, were found to be significantly lower the rest of the channels for six one-minute EEG segments prior to seizure onset and nine one-minute EEG segments of an awake state. The half-lives of volatility for RAST3 and RAST4 were not significantly different to the non-seizure channels for ten one-minute segments of sleep and ten one-minute segments of sleep-to-awake states. The estimates for the half-lives were consistent for randomly selected one-minute EEG segments. Conclusions: The use of GARCH models may be a useful tool in determining hidden properties in epileptiform EEGs that may lead to better understanding of the seizure generating process.
PLA2 Inhibitor Varespladib as an Alternative to the Antivenom Treatment for Bites from Nikolsky’s Viper Vipera berus nikolskii
Authors: Zinenko Oleksandr , Tovstukha Igor , Korniyenko Yevgen
Published: June 2020

Although envenoming by a small East European species of viper is rarely severe, and only exceptionally fatal, lack of specific antivenom stocks in a few areas within this region and possible severe side effects of antivenom application leave most bites to be treated only with antihistamines and supportive therapy. Varespladib is an effective inhibitor of snake phospholipase, and, as such, it could be considered as first-line therapy. The Nikolsky’s viper venom contains an extremely high concentration of phospholipase A2 (PLA2), responsible for the toxic effects of the venom, as well as minor amounts of other toxins. If Varespladib can successfully inhibit PLA2 activity, the Nikolsky’s viper could be one of the first venomous snakes having an antitoxin-specific treatment regimen. To assess that, Varespladib was administered alone subcutaneously to adult male CD-1 mice (8 mg/kg) and compared to mice exposed to Vipera berus nikolskii crude venom (8 mg/kg = 10 LD50) or a combination of Varespladib and the same amount of the venom. Experimental animals were monitored for the presence of envenoming symptoms and mortality for 48 h after injection. Eighty percent of mice receiving both Varespladib and venom survived, while 100% of the control group receiving venom alone died within 4 h. Experimental results are consistent with Varespladib acting as an effective antitoxin in the mouse model against Nikolsky’s viper venom. Further studies are needed under experimental conditions that more closely resemble natural envenoming (i.e., delayed administration).
The Procoagulant Snake Venom Serine Protease Potentially Having a Dual, Blood Coagulation Factor V and X-Activating Activity
Authors: Latinović Zorica , Leonardi Adrijana , Koh Cho Yeow , Kini R. Manjunatha , Trampuš Bakija Alenka , Pungerčar Jože , Križaj Igor
Published: June 2020

A procoagulant snake venom serine protease was isolated from the venom of the nose-horned viper (Vipera ammodytes ammodytes). This 34 kDa glycoprotein, termed VaaSP-VX, possesses five kDa N-linked carbohydrates. Amino acid sequencing showed VaaSP-VX to be a chymotrypsin-like serine protease. Structurally, it is highly homologous to VaaSP-6 from the same venom and to nikobin from the venom of Vipera nikolskii, neither of which have known functions. VaaSP-VX does not affect platelets. The specific proteolysis of blood coagulation factors X and V by VaaSP-VX suggests that its blood-coagulation-inducing effect is due to its ability to activate these two blood coagulation factors, which following activation, combine to form the prothrombinase complex. VaaSP-VX may thus represent the first example of a serine protease with such a dual activity, which makes it a highly suitable candidate to replace diluted Russell’s viper venom in lupus anticoagulant testing, thus achieving greater reliability of the analysis. As a blood-coagulation-promoting substance that is resistant to serpin inhibition, VaaSP-VX is also interesting from the therapeutic point of view for treating patients suffering from hemophilia.
RTX-Toxins
Authors: Benz Roland
Published: June 2020

RTX-Toxins (Repeats in ToXin) are members of a rapidly expanding family of proteins [...]
Endothelial Damage, Inflammation and Immunity in Chronic Kidney Disease
Authors: Diaz-Ricart Maribel , Torramade-Moix Sergi , Pascual Georgina , Palomo Marta , Moreno-Castaño Ana Belen , Martinez-Sanchez Julia , Vera Manel , Cases Aleix , Escolar Gines
Published: June 2020

Chronic kidney disease (CKD) patients have an accelerated atherosclerosis, increased risk of thrombotic-ischemic complications, and excessive mortality rates when compared with the general population. There is also evidence of an endothelial damage in which the proinflammatory state, the enhanced oxidative stress, or the accumulation of toxins due to their reduced renal clearance in uremia play a role. Further, there is evidence that uremic endothelial cells are both involved in and victims of the activation of the innate immunity. Uremic endothelial cells produce danger associated molecular patterns (DAMPS), which by binding to specific pattern recognition receptors expressed in multiple cells, including endothelial cells, induce the expression of adhesion molecules, the production of proinflammatory cytokines and an enhanced production of reactive oxygen species in endothelial cells, which constitute a link between immunity and inflammation. The connection between endothelial damage, inflammation and defective immunity in uremia will be reviewed here.
Therapeutic Targeting of Aristolochic Acid Induced Uremic Toxin Retention, SMAD 2/3 and JNK/ERK Pathways in Tubulointerstitial Fibrosis: Nephroprotective Role of Propolis in Chronic Kidney Disease
Authors: Chang Jia-Feng , Hsieh Chih-Yu , Lu Kuo-Cheng , Chen Yue-Wen , Liang Shih-Shin , Lin Chih-Cheng , Hung Chi-Feng , Liou Jian-Chiun , Wu Mai-Szu
Published: June 2020

The nephrotoxicity of aristolochic acids (AAs), p-cresyl sulfate (PCS) and indoxyl sulfate (IS) were well-documented, culminating in tubulointerstitial fibrosis (TIF), advanced chronic kidney disease (CKD) and fatal urothelial cancer. Nonetheless, information regarding the attenuation of AAs-induced nephropathy (AAN) and uremic toxin retention is scarce. Propolis is a versatile natural product, exerting anti-oxidant, anti-cancer and anti-fibrotic properties. We aimed to evaluate nephroprotective effects of propolis extract (PE) in a murine model. AAN was developed to retain circulating PCS and IS using C57BL/6 mice, mimicking human CKD. The kidney sizes/masses, renal function indicators, plasma concentrations of PCS/IS, tissue expressions of TIF, α-SMA, collagen IaI, collagen IV and signaling pathways in transforming growth factor-β (TGF-β) family were analyzed among the control, PE, AAN, and AAN-PE groups. PE ameliorated AAN-induced renal atrophy, renal function deterioration, TIF, plasma retention of PCS and IS. PE also suppressed α-SMA expression and deposition of collagen IaI and IV in the fibrotic epithelial-mesenchymal transition. Notably, PE treatment in AAN model inhibited not only SMAD 2/3-dependent pathways but also SMAD-independent JNK/ERK activation in the signaling cascades of TGF-β family. Through disrupting fibrotic epithelial-mesenchymal transition and TGF-β signaling transduction pathways, PE improves TIF and thereby facilitates renal excretion of PCS and IS in AAN. In light of multi-faced toxicity of AAs, PE may be capable of developing a new potential drug to treat CKD patients exposed to AAs.
An Anti-Cancer Peptide LVTX-8 Inhibits the Proliferation and Migration of Lung Tumor Cells by Regulating Causal Genes’ Expression in p53-Related Pathways
Authors: Zhang Peng , Yan Yujie , Wang Junting , Dong Xiaoping , Zhang Gaihua , Zeng Yong , Liu Zhonghua
Published: June 2020

Spider venom has been found to show its anticancer activity in a variety of human malignancies, including lung cancer. In this study, we investigated the anti-cancer peptide toxin LVTX-8, with linear amphipathic alpha-helical conformation, designed and synthesized from the cDNA library of spider Lycosa vittata. Multiple cellular methods, such as CCK-8 assay, flow cytometry, colony formation assay, Transwell invasion and migration assay, were performed to detect peptide-induced cell growth inhibition and anti-metastasis in lung cancer cells. Our results demonstrated that LVTX-8 displayed strong cytotoxicity and anti-metastasis towards lung cancer in vitro. Furthermore, LVTX-8 could suppress the growth and metastasis of lung cancer cells (A549 and H460) in nude mouse models. Transcriptomics, integrated with multiple bioinformatics analysis, suggested that the molecular basis of the LVTX-8-mediated inhibition of cancer cell growth and metastasis manifested in two aspects: Firstly, it could restrain the activity of cancer cell division and migration through the functional pathways, including “p53 hypoxia pathway” and “integrin signaling”. Secondly, it could regulate the expression level of apoptotic-related proteins, which may account for programmed apoptosis of cancer cells. Taken together, as an anticancer peptide with high efficiency and acceptable specificity, LVTX-8 may become a potential precursor of a therapeutic agent for lung cancer in the future.
Reduced-Beclin1-Expressing Mice Infected with Zika-R103451 and Viral-Associated Pathology during Pregnancy
Authors: Karuppan Mohan Kumar Muthu , Ojha Chet Raj , Rodriguez Myosotys , Lapierre Jessica , Aman M. Javad , Kashanchi Fatah , Toborek Michal , Nair Madhavan , El-Hage Nazira
Published: June 2020

Here, we used a mouse model with defective autophagy to further decipher the role of Beclin1 in the infection and disease of Zika virus (ZIKV)-R103451. Hemizygous (Becn1+/−) and wild-type (Becn1+/+) pregnant mice were transiently immunocompromised using the anti-interferon alpha/beta receptor subunit 1 monoclonal antibody MAR1-5A3. Despite a low mortality rate among the infected dams, 25% of Becn1+/− offspring were smaller in size and had smaller, underdeveloped brains. This phenotype became apparent after 2-to 3-weeks post-birth. Furthermore, the smaller-sized pups showed a decrease in the mRNA expression levels of insulin-like growth factor (IGF)-1 and the expression levels of several microcephaly associated genes, when compared to their typical-sized siblings. Neuronal loss was also noticeable in brain tissues that were removed postmortem. Further analysis with murine mixed glia, derived from ZIKV-infected Becn1+/− and Becn1+/+ pups, showed greater infectivity in glia derived from the Becn1+/− genotype, along with a significant increase in pro-inflammatory molecules. In the present study, we identified a link by which defective autophagy is causally related to increased inflammatory molecules, reduced growth factor, decreased expression of microcephaly-associated genes, and increased neuronal loss. Specifically, we showed that a reduced expression of Beclin1 aggravated the consequences of ZIKV infection on brain development and qualifies Becn1 as a susceptibility gene of ZIKV congenital syndrome.
Deciphering the Mechanisms of Improved Immunogenicity of Hypochlorous Acid-Treated Antigens in Anti-Cancer Dendritic Cell-Based Vaccines
Authors: Graciotti Michele , Marino Fabio , Pak HuiSong , Baumgaertner Petra , Thierry Anne-Christine , Chiffelle Johanna , Perez Marta A. S. , Zoete Vincent , Harari Alexandre , Bassani-Sternberg Michal , Kandalaft Lana E.
Published: June 2020

Hypochlorous acid (HOCl)-treated whole tumor cell lysates (Ox-L) have been shown to be more immunogenic when used as an antigen source for therapeutic dendritic cell (DC)-based vaccines, improving downstream immune responses both in vitro and in vivo. However, the mechanisms behind the improved immunogenicity are still elusive. To address this question, we conducted a proteomic and immunopeptidomics analyses to map modifications and alterations introduced by HOCl treatment using a human melanoma cell line as a model system. First, we show that one-hour HOCl incubation readily induces extensive protein oxidation, mitochondrial biogenesis, and increased expression of chaperones and antioxidant proteins, all features indicative of an activation of oxidative stress-response pathways. Characterization of the DC proteome after loading with HOCl treated tumor lysate (Ox-L) showed no significant difference compared to loading with untreated whole tumor lysate (FT-L). On the other hand, detailed immunopeptidomic analyses on monocyte-derived DCs (mo-DCs) revealed a great increase in human leukocyte antigen class II (HLA-II) presentation in mo-DCs loaded with Ox-L compared to the FT-L control. Further, 2026 HLA-II ligands uniquely presented on Ox-L-loaded mo-DCs were identified. In comparison, identities and intensities of HLA class I (HLA-I) ligands were overall comparable. We found that HLA-II ligands uniquely presented by DCs loaded with Ox-L were more solvent exposed in the structures of their source proteins, contrary to what has been hypothesized so far. Analyses from a phase I clinical trial showed that vaccinating patients using autologous Ox-L as an antigen source efficiently induces polyfunctional vaccine-specific CD4+ T cell responses. Hence, these results suggest that the increased immunogenicity of Ox-L is, at least in part, due to qualitative and quantitative changes in the HLA-II ligandome, potentially leading to an increased HLA-II dependent stimulation of the T cell compartment (i.e., CD4+ T cell responses). These results further contribute to the development of more effective and immunogenic DC-based vaccines and to the molecular understanding of the mechanism behind HOCl adjuvant properties.
Novel Ensembles of Deep Learning Neural Network and Statistical Learning for Flash-Flood Susceptibility Mapping
Authors: Costache Romulus , Ngo Phuong Thao Thi , Bui Dieu Tien
Published: June 2020

This study aimed to assess flash-flood susceptibility using a new hybridization approach of Deep Neural Network (DNN), Analytical Hierarchy Process (AHP), and Frequency Ratio (FR). A catchment area in south-eastern Romania was selected for this proposed approach. In this regard, a geospatial database of the flood with 178 flood locations and with 10 flash-flood predictors was prepared and used for this proposed approach. AHP and FR were used for processing and coding the predictors into a numeric format, whereas DNN, which is a powerful and state-of-the-art probabilistic machine leaning, was employed to build an inference flash-flood model. The reliability of the models was verified with the help of Receiver Operating Characteristic (ROC) Curve, Area Under Curve (AUC), and several statistical measures. The result shows that the two proposed ensemble models, DNN-AHP and DNN-FR, are capable of predicting future flash-flood areas with accuracy higher than 92%; therefore, they are a new tool for flash-flood studies.
Estimation of Flood Travel Time in River Network of the Middle Yellow River, China
Authors: He Li
Published: June 2020

The flood travel time (FTT) along the Longmen-Tongguan Reach, part of the stem channel of the Middle Yellow River, is shorter than 30 h, and estimating the FTT of different discharges propagating from Wubu Hydrology Station to Tongguan Hydrology Station is necessary. However, the propagation of floods in this river network, the main channel of the Wubu-Tongguan Reach and related tributaries, has rarely been analyzed due to the lack of geometry data. Thus, a one-dimensional (1D) dynamic model was selected to simulate the FTT along the WT reach. Firstly, the 1986 flood event was selected to calibrate the physical parameters in the hydraulic model. Secondly, the FTT with different discharges (500–9000 m3/s) were estimated with calibrated parameters. Thirdly, an empirical formula based on simulated results was fitted. This empirical formula could be used to describe the relation between discharges, distances to Tongguan Hydrology Station, and the FTT. Analyses showed that the discharges with minimum FTT were different for different tributaries. For the river reach between Wubu Hydrology Station and the Wuding River, the discharge and corresponding minimum FTT were 6000 m3/s and approximately 30.4–34 h, respectively. For the river reach between the Zhouchuan and Qingjian Rivers, the discharge and FTT were 3000–3500 m3/s and 21–26.8 h, respectively. The formula can be used to estimate the FTT of flood events, which would be cost-saving and time-saving for river management. Sensitivity analyses indicated that the FTT were sensitive to the Tongguan elevation and Manning’s roughness coefficient in the main channel.