bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Depth on the Morphology, Bacterial Clearance, and Respiration of the Mediterranean Sponge Chondrosia reniformis (Nardo, 1847)
Authors: Gökalp Mert , Kooistra Tjitske , Rocha Miguel Soares , Silva Tiago H. , Osinga Ronald , Murk AlberTinka J. , Wijgerde Tim
Published: July 2020

To support the successful application of sponges for water purification and collagen production, we evaluated the effect of depth on sponge morphology, growth, physiology, and functioning. Specimens of Eastern Mediterranean populations of the sponge Chondrosia reniformis (Nardo, 1847) (Demospongiae, Chondrosiida, Chondrosiidae) were reciprocally transplanted between 5 and 20 m depth within the Kaş-Kekova Marine Reserve Area. Control sponges at 5 m had fewer but larger oscula than their conspecifics at 20 m, and a significant inverse relationship between the osculum density and size was found in C. reniformis specimens growing along a natural depth gradient. Sponges transplanted from 20 to 5 m altered their morphology to match the 5 m control sponges, producing fewer but larger oscula, whereas explants transplanted from 5 to 20 m did not show a reciprocal morphological plasticity. Despite the changes in morphology, the clearance, respiration, and growth rates were comparable among all the experimental groups. This indicates that depth-induced morphological changes do not affect the overall performance of the sponges. Hence, the potential for the growth and bioremediation of C. reniformis in mariculture is not likely to change with varying culture depth. The collagen content, however, was higher in shallow water C. reniformis compared to deeper-growing sponges, which requires further study to optimize collagen production.
Influence of the Feed Powder Composition in Mechanical Properties of AlN-Nano-Reinforced Aluminium Composites Coatings Deposited by Reactive Direct Laser Deposition
Authors: Riquelme Ainhoa , Rodrigo Pilar , Escalera-Rodriguez María Dolores , García-Fogeda Pablo , Rams Joaquín
Published: July 2020

Aluminium matrix composite coatings reinforced with AlN nanopaticles have been manufactured by direct laser deposition on an AA6082 alloy substrate. The reinforcement of the composite has been generated by the direct nitridation reaction of the feed powder with the carrier gas (N2) heated by an HPDL beam during the fabrication of the coating. The coating obtained consists of nano-sized AlN particles in an aluminium matrix, and the crystalline structure of the obtained AlN depends on the characteristics of the powder used. In this work, the influence of the feed powder composition is studied by comparison among pure aluminium, Al12-Si alloy, and AA6061 alloy, on the formation of AlN and its crystalline structure. A correlation was established between the temperature distribution reached by the particles, their composition, and the nitridation reaction mechanisms. The effect of the reinforcement was evaluated by comparing the microstructure and mechanical properties (microhardness, nanoindentation) of the composite costing with non-reinforced Al coatings and uncoated AA6082. Al/AlN composite coatings with improved properties were achieved, reaching hardness values that were 65% higher than coatings without reinforcement.
Feeling Machine for Process Monitoring of Turning Hybrid Solid Components
Authors: Denkena Berend , Bergmann Benjamin , Witt Matthias
Published: July 2020

The realization of the increasing automation of production systems requires the guarantee of process security as well as the resulting workpiece quality. For this purpose, monitoring systems are used, which monitor the machining based on machine control signals and external sensors. These systems are challenged by innovative design concepts such as hybrid components made of different materials, which lead to new disturbance variables in the process. Therefore, it is important to obtain as much process information as possible in order to achieve a robust and sensitive evaluation of the machining. Feeling machines with force sensing capabilities represent a promising approach to assist the monitoring. This paper provides, for the first time, an overview of the suitability of the feeling machine for process monitoring during turning operations. The process faults tool breakage, tool wear, and the variation of the material transition position of hybrid shafts that were researched and compared with a force dynamometer. For the investigation, longitudinal turning processes with shafts made of EN AW-6082 and 20MnCr5 were carried out. The results show the feeling machine is sensitive to all kinds of examined errors and can compete with a force dynamometer, especially for roughing operations.
Adjustment of Isothermal Transformation Diagrams Using Finite-Element Optimization of the Jominy Test
Authors: Irani Missam , Chung Sukhwan , Kim Mincheol , Lee Kwangoh , Joun Mansoo
Published: July 2020

A practical method for adjusting and optimizing isothermal transformation (IT) diagrams using the Jominy test is presented. The method is based on a finite-element optimization procedure, which iteratively minimizes the error between the target phase fractions and the corresponding finite-element solutions at the sample points using an optimization tool. A standard Jominy test of AISI 52100 bearing steel is used to investigate the feasibility and reliability of the method. Three optimization parameters for each IT diagram curve are mathematically applied to the modified Kirkaldy model. These parameters are the design variables in the optimization. The curves obtained from the modified Kirkaldy model are used as the initial guesses in the optimization and they approach the experimental IT diagram by minimizing the error. Good agreement is observed between the optimized diagram and the experimental diagram reported in the literature. The predicted phase fractions using the experimental IT diagram, the IT diagram obtained from the modified Kirkaldy model, and those obtained from the optimized model are compared and demonstrate that the adjustment or optimization procedure significantly improves the accuracy of the predicted phase fraction of the model. The applicability of the method is investigated in a practical case study.
Regulatory T Cell Metabolism in Atherosclerosis
Authors: Baardman Jeroen , Lutgens Esther
Published: July 2020

Regulatory T cells (Tregs) are capable of suppressing excessive immune responses to prevent autoimmunity and chronic inflammation. Decreased numbers of Tregs and impaired suppressive function are associated with the progression of atherosclerosis, a chronic inflammatory disease of the arterial wall and the leading cause of cardiovascular disease. Therefore, therapeutic strategies to improve Treg number or function could be beneficial to preventing atherosclerotic disease development. A growing body of evidence shows that intracellular metabolism of Tregs is a key regulator of their proliferation, suppressive function, and stability. Here we evaluate the role of Tregs in atherosclerosis, their metabolic regulation, and the links between their metabolism and atherosclerosis.
Development and Validation of a Highly Sensitive LC-MS/MS Method for the Analysis of Bile Acids in Serum, Plasma, and Liver Tissue Samples
Authors: Gómez Cristina , Stücheli Simon , Kratschmar Denise V. , Bouitbir Jamal , Odermatt Alex
Published: July 2020

Bile acids control lipid homeostasis by regulating uptake from food and excretion. Additionally, bile acids are bioactive molecules acting through receptors and modulating various physiological processes. Impaired bile acid homeostasis is associated with several diseases and drug-induced liver injury. Individual bile acids may serve as disease and drug toxicity biomarkers, with a great demand for improved bile acid quantification methods. We developed, optimized, and validated an LC-MS/MS method for quantification of 36 bile acids in serum, plasma, and liver tissue samples. The simultaneous quantification of important free and taurine- and glycine-conjugated bile acids of human and rodent species has been achieved using a simple workflow. The method was applied to a mouse model of statin-induced myotoxicity to assess a possible role of bile acids. Treatment of mice for three weeks with 5, 10, and 25 mg/kg/d simvastatin, causing adverse skeletal muscle effects, did not alter plasma and liver tissue bile acid profiles, indicating that bile acids are not involved in statin-induced myotoxicity. In conclusion, the established LC-MS/MS method enables uncomplicated sample preparation and quantification of key bile acids in serum, plasma, and liver tissue of human and rodent species to facilitate future studies of disease mechanisms and drug-induced liver injury.
Transcriptional Regulation in Non-Alcoholic Fatty Liver Disease
Authors: Steensels Sandra , Qiao Jixuan , Ersoy Baran A.
Published: July 2020

Obesity is the primary risk factor for the pathogenesis of non-alcoholic fatty liver disease (NAFLD), the worldwide prevalence of which continues to increase dramatically. The liver plays a pivotal role in the maintenance of whole-body lipid and glucose homeostasis. This is mainly mediated by the transcriptional activation of hepatic pathways that promote glucose and lipid production or utilization in response to the nutritional state of the body. However, in the setting of chronic excessive nutrition, the dysregulation of hepatic transcriptional machinery promotes lipid accumulation, inflammation, metabolic stress, and fibrosis, which culminate in NAFLD. In this review, we provide our current understanding of the transcription factors that have been linked to the pathogenesis and progression of NAFLD. Using publicly available transcriptomic data, we outline the altered activity of transcription factors among humans with NAFLD. By expanding this analysis to common experimental mouse models of NAFLD, we outline the relevance of mouse models to the human pathophysiology at the transcriptional level.
Editorial for the Special Issue on Silicon Photonics Bloom
Authors: Zhao Qiancheng , Boyraz Ozdal
Published: July 2020

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Molecular Detection of Avian Pathogenic Escherichia coli (APEC) for the First Time in Layer Farms in Bangladesh and Their Antibiotic Resistance Patterns
Authors: Ievy Samina , Islam Md. Saiful , Sobur Md. Abdus , Talukder Mithun , Rahman Md. Bahanur , Khan Mohammad Ferdousur Rahman , Rahman Md. Tanvir
Published: July 2020

Avian pathogenic Escherichia coli (APEC) causes significant economic losses in poultry industries. Here, we determined for the first time in Bangladesh, the prevalence of APEC-associated virulence genes in E. coli isolated from layer farms and their antibiotic resistance patterns. A total of 99 samples comprising internal organs, feces, and air were collected from 32 layer farms. Isolation was performed by culturing samples on eosin–methylene blue agar plates, while the molecular detection of APEC was performed by PCR, and antibiograms were performed by disk diffusion. Among the samples, 36 were positive for the APEC-associated virulence genes fimC, iucD, and papC. Out of 36 isolates, 7, 18, and 11 were positive, respectively, for three virulence genes (papC, fimC, and iucD), two virulence genes, and a single virulence gene. Although the detection of virulence genes was significantly higher in the internal organs, the air and feces were also positive. The antibiograms revealed that all the isolates (100%) were resistant to ampicillin and tetracycline; 97.2%, to chloramphenicol and erythromycin; 55.5%, to enrofloxacin; 50.0%, to norfloxacin and ciprofloxacin; 19.4%, to streptomycin; 11.1%, to colistin; and 8.33%, to gentamicin. Interestingly, all the isolates were multidrug-resistant (MDR). Spearman’s rank correlation coefficient analysis revealed the strongest significant correlation between norfloxacin and ciprofloxacin resistance. This is the first study in Bangladesh describing the molecular detection of APEC in layer farms. Isolated APEC can now be used for detailed genetic characterization and assessing the impact on public health.
Extrinsic Factors Shaping the Skin Microbiome
Authors: Moskovicz Veronica , Gross Adi , Mizrahi Boaz
Published: July 2020

Human skin, our most environmentally exposed organ, is colonized by a vast array of microorganisms constituting its microbiome. These bacterial communities are crucial for the fulfillment of human physiological functions such as immune system modulation and epidermal development and differentiation. The structure of the human skin microbiome is established during the early life stages, starting even before birth, and continues to be modulated throughout the entire life cycle, by multiple host-related and environmental factors. This review focuses on extrinsic factors, ranging from cosmetics to the environment and antibacterial agents, as forces that impact the human skin microbiome and well-being. Assessing the impact of these factors on the skin microbiome will help elucidate the forces that shape the microbial populations we coexist with. Furthermore, we will gain additional insight into their tendency to stimulate a healthy environment or to increase the propensity for skin disorder development.
Influence of Seawater on the Degree of Entrainment in the Flotation of a Synthetic Copper Ore
Authors: Gutierrez Leopoldo , Betancourt Fernando , Uribe Lina , Maldonado Miguel
Published: July 2020

Froth flotation is a process in which hydrophobic particles attach to bubbles forming particle–bubble aggregates, which are transported to the top section of the cell where they overflow to form the concentrate. Particles also reach the concentrate by entrainment, which is a non-selective process that leads to low concentrate grades. The objective of this work was to study and compare the degree of entrainment measured using three methods, in fresh and seawater, and using methyl isobutyl carbinol (MIBC) and DF-250 as frothers. The experimental results indicated that the degree of entrainment decreased in seawater. Besides, water recovery was lower in the experiments with seawater regardless of the frother that was used in the experiments, which correlated with the observed low degrees of entrainment. It is proposed that the reduction of entrainment and water recovery in seawater can be explained by a reduction of air recovery and/or more bubble coalescence in the froth. It is also proposed that surfactant diffusion/convection from the lamellae to the Plateau borders in the froth is reduced in seawater, which reduces the surface tension gradients, and thus the restoring liquid flow from the Plateau borders to the lamellae.
Optimisation of Sporosori Purification and Protein Extraction Techniques for the Biotrophic Protozoan Plant Pathogen Spongospora subterranea
Authors: Balotf Sadegh , Wilson Richard , Tegg Robert S. , Nichols David S. , Wilson Calum R.
Published: July 2020

Spongospora subterranea is a soil-borne plant pathogen responsible for the economically significant root and powdery scab diseases of potato. However, the obligate biotrophic nature of S. subterranea has made the detailed study of the pathogen problematic. Here, we first compared the benefits of sporosori partial purification utilizing Ludox® gradient centrifugation. We then undertook optimization efforts for protein isolation comparing the use of a urea buffer followed by single-pot solid-phase-enhanced sample preparation (SP3) and a sodium dodecyl sulphate (SDS) buffer followed by suspension-trapping (S-Trap). Label-free, quantitative proteomics was then used to evaluate the efficiency of the sporosori purification and the protein preparation methods. The purification protocol produced a highly purified suspension of S. subterranea sporosori without affecting the viability of the spores. The results indicated that the use of a combination of SDS and S-Trap for sample clean-up and digestion obtained a significantly higher number of identified proteins compared to using urea and SP3, with 218 and 652 proteins identified using the SP3 and S-Trap methods, respectively. The analysis of proteins by mass spectrometry showed that the number of identified proteins increased by approximately 40% after the purification of spores by Ludox®. These results suggested a potential use of the described spore purification and protein preparation methods for the proteomics study of obligate biotrophic pathogens such as S. subterranea.
Ameliorated Mechanical and Dielectric Properties of Heat-Resistant Radome Cyanate Composites
Authors: Li Hou-Yu , Li Chang-Ming , Gao Jun-Guo , Sun Wei-Feng
Published: July 2020

In order to improve the mechanical and dielectric properties of radome cyanate, a synergistic reinforcement method is employed to develop a resin-based ternary-composite with high heat-resistance and preferable radar-band transmission, which is expected to be applied to fabricate radomes capable of resisting high temperature and strong electric field. According to copolymerization characteristics and self-curing mechanism, epoxy resin (EP) and bismaleimide (BMI) are employed as reinforcements mixed into a cyanate ester (CE) matrix to prepare CE/BMI/EP composites of a heat-resistant radome material by high-temperature viscous-flow blending methods under the catalysis of aluminum acetylpyruvate. The crystallization temperature, transition heat, and reaction rate of cured polymers were tested to analyze heat-resistance characteristics and evaluate material synthesis processes. Scanning electron microscopy was used to characterize the micro-morphology of tensile fracture, which was combined with the tensile strength test and dynamic thermomechanical analysis to investigate the composite modifications on tenacity and rigidity. Weibull statistics were performed to analyze the experimental results of the dielectric breakdown field, and the dielectric-polarization and wave-transmission performances were investigated according to alternative current dielectric spectra. Compared with the pure CE and the CE composites individually reinforced by EP or BMI, the CE/BMI/EP composite acquires the most significant amelioration in both the mechanical and electrical insulation performances as indicated by the breaking elongation and dielectric breakdown strength being simultaneously improved by 40%, which are consistently manifested by the obviously increased transverse lines uniformly distributed on the fracture cross-section. Furthermore, the glass-transition temperature of CE/BMI/EP composite reaches the highest values of nearly 300 °C, with the relative dielectric constant and dielectric loss being mostly reduced to less than 3.2 and 0.01, respectively. The experimental results demonstrate that the CE/BMI/EP composite is a highly-qualified wave-transmission material with preferences in mechanical, thermostability, and electrical insulation performances, suggesting its prospective applications in low-frequency transmittance radomes.
5-Aryl-2-(3,5-dialkyl-4-hydroxyphenyl)-4,4-dimethyl-4H-imidazole 3-Oxides and Their Redox Species: How Antioxidant Activity of 1-Hydroxy-2,5-dihydro-1H-imidazoles Correlates with the Stability of Hybrid Phenoxyl–Nitroxides
Authors: Amitina Svetlana A. , Zaytseva Elena V. , Dmitrieva Natalya A. , Lomanovich Alyona V. , Kandalintseva Natalya V. , Ten Yury A. , Artamonov Ilya A. , Markov Alexander F. , Mazhukin Dmitrii G.
Published: July 2020

Cyclic nitrones of the imidazole series, containing a sterically hindered phenol group, are promising objects for studying antioxidant activity; on the other hand, they can form persistent hybrid phenoxyl–nitroxyl radicals (HPNs) upon oxidation. Here, a series of 5-aryl-4,4-dimethyl-4H-imidazole 3-oxides was obtained by condensation of aromatic 2-hydroxylaminoketones with 4-formyl-2,6-dialkylphenols followed by oxidation of the initially formed N-hydroxy derivatives. It was shown that the antioxidant activity of both 1-hydroxy-2,5-dihydroimidazoles and 4H-imidazole 3-oxides increases with a decrease in steric volume of the alkyl substituent in the phenol group, while the stability of the corresponding HPNs generated from 4H-imidazole 3-oxides reveals the opposite tendency.
The Influence of Single, Tandem, and Clustered DNA Damage on the Electronic Properties of the Double Helix: A Theoretical Study
Authors: Karwowski Bolesław T.
Published: July 2020

Oxidatively generated damage to DNA frequently appears in the human genome as the effect of aerobic metabolism or as the result of exposure to exogenous oxidizing agents, such as ionization radiation. In this paper, the electronic properties of single, tandem, and clustered DNA damage in comparison with native ds-DNA are discussed as a comparative analysis for the first time. A single lesion—8-oxo-7,8-dihydro-2′-deoxyguanosine (Goxo), a tandem lesion—(5′S) and (5′R) 5′,8-cyclo-2′-deoxyadenosine (cdA), and the presence of both of them in one helix turn as clustered DNA damage were chosen and taken into consideration. The lowest vertical and adiabatic potential (VIP ~ 5.9 and AIP ~ 5.5 eV, respectively) were found for Goxo, independently of the discussed DNA lesion type and their distribution within the double helix. Moreover, the VIP and AIP were assigned for ds-trimers, ds- dimers and single base pairs isolated from parental ds-hexamers in their neutral and cationic forms. The above results were confirmed by the charge and spin density population, which revealed that Goxo can be considered as a cation radical point of destination independently of the DNA damage type (single, tandem, or clustered). Additionally, the different influences of cdA on the charge transfer rate were found and discussed in the context of tandem and clustered lesions. Because oligonucleotide lesions are effectively produced as a result of ionization factors, the presented data in this article might be valuable in developing a new scheme of anticancer radiotherapy efficiency.
Porin from Marine Bacterium Marinomonas primoryensis KMM 3633T: Isolation, Physico-Chemical Properties, and Functional Activity
Authors: Novikova Olga D. , Khomenko Valentina A. , Kim Natalia Yu. , Likhatskaya Galina N. , Romanenko Lyudmila A. , Aksenova Ekaterina I. , Kunda Marina S. , Ryzhova Natalia N. , Portnyagina Olga Yu. , Solov’eva Tamara F. , Voronina Olga L.
Published: July 2020

Marinomonas primoryensis KMM 3633T, extreme living marine bacterium was isolated from a sample of coastal sea ice in the Amursky Bay near Vladivostok, Russia. The goal of our investigation is to study outer membrane channels determining cell permeability. Porin from M. primoryensis KMM 3633T (MpOmp) has been isolated and characterized. Amino acid analysis and whole genome sequencing were the sources of amino acid data of porin, identified as Porin_4 according to the conservative domain searching. The amino acid composition of MpOmp distinguished by high content of acidic amino acids and low content of sulfur-containing amino acids, but there are no tryptophan residues in its molecule. The native MpOmp existed as a trimer. The reconstitution of MpOmp into black lipid membranes demonstrated its ability to form ion channels whose conductivity depends on the electrolyte concentration. The spatial structure of MpOmp had features typical for the classical gram-negative porins. However, the oligomeric structure of isolated MpOmp was distinguished by very low stability: heat-modified monomer was already observed at 30 °C. The data obtained suggest the stabilizing role of lipids in the natural membrane of marine bacteria in the formation of the oligomeric structure of porin.
Discovery of 4-Anilinoquinolinylchalcone Derivatives as Potential NRF2 Activators
Authors: Kao Yu-Tse , Chen Yi-Siao , Tang Kai-Wei , Lee Jin-Ching , Tseng Chih-Hua , Tzeng Cherng-Chyi , Yen Chia-Hung , Chen Yeh-Long
Published: July 2020

Activation of nuclear factor erythroid-2-related factor 2 (NRF2) has been proven to be an effective means to prevent the development of cancer, and natural curcumin stands out as a potent NRF2 activator and cancer chemopreventive agent. In this study, we have synthesized a series of 4-anilinoquinolinylchalcone derivatives, and used a NRF2 promoter-driven firefly luciferase reporter stable cell line, the HaCaT/ARE cells, to screen a panel of these compounds. Among them, (E)-3-{4-[(4-acetylphenyl)amino]quinolin-2-yl}-1-(4-fluorophenyl)prop-2-en-1-one (13b) significantly increased NRF2 activity in the HaCaT cell with a half maximal effective concentration (EC50) value of 1.95 μM. Treatment of compound 13b upregulated HaCaT cell NRF2 expression at the protein level. Moreover, the mRNA level of NRF2 target genes, heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and glucose-6-phosphate dehydrogenase (G6PD) were significantly increased in HaCaT cells upon the compound 13b treatment. The molecular docking results exhibited that the small molecule 13b is well accommodated by the bound region of Kelch-like ECH-associated protein 1 (Keap1)-Kelch and NRF2 through stable hydrogen bonds and hydrophobic interaction, which contributed to the enhancement of affinity and stability between the ligand and receptor. Compound 13b has been identified as the lead compound for further structural optimization.
Synthesis and Immunological Evaluation of a Single Molecular Construct MUC1 Vaccine Containing l-Rhamnose Repeating Units
Authors: Hossain Md Kamal , Vartak Abhishek , Sucheck Steven J. , Wall Katherine A.
Published: July 2020

A rhamnose targeting strategy for generating effective anticancer vaccines was successful in our previous studies. We showed that by utilizing natural anti-rhamnose antibodies, a rhamnose-containing vaccine can be targeted to antigen-presenting cells, such as dendritic cells. In this case, rhamnose (Rha) was linked directly to the liposomes bearing the antigen. However, in the current approach, we conjugated a multivalent Tri-Rha ligand with the antigen itself, making it a single component vaccine construct, unlike the previous two-component vaccine construct where Rha cholesterol and Mucin1 (MUC1) antigen were both linked separately to the liposomes. Synthesis required the development of a linker for coupling of the Rha-Ser residues. We compared those two systems in a mouse model and found increased production of anti-MUC1 antibodies and more primed antigen-specific CD4+ T cells in both of the targeted approaches when compared to the control group, suggesting that this one-component vaccine construct could be a potential design used in our MUC1 targeting mechanisms.
Phytochemical Analysis and Trypanocidal Activity of Marrubium incanum Desr.
Authors: Frezza Claudio , Venditti Alessandro , Bianco Armandodoriano , Serafini Mauro , Pitorri Massimo , Sciubba Fabio , Di Cocco Maria Enrica , Spinozzi Eleonora , Cappellacci Loredana , Hofer Anders , Maggi Filippo , Petrelli Riccardo
Published: July 2020

The rationale inspiring the discovery of lead compounds for the treatment of human parasitic protozoan diseases from natural sources is the well-established use of medicinal plants in various systems of traditional medicine. On this basis, we decided to select an overlooked medicinal plant growing in central Italy, Marrubium incanum Desr. (Lamiaceae), which has been used as a traditional remedy against protozoan diseases, and to investigate its potential against Human African trypanosomiasis (HAT). For this purpose, we assayed three extracts of different polarities obtained from the aerial parts of M. incanum—namely, water (MarrInc-H2O), ethanol (MarrInc-EtOH) and dichloromethane (MarrInc-CH2Cl2)—against Trypanosoma brucei (TC221), with the aim to discover lead compounds for the development of antitrypanosomal drugs. Their selectivity index (SI) was determined on mammalian cells (BALB/3T3 mouse fibroblasts) as a counter-screen for toxicity. The preliminary screening selected the MarrInc-CH2Cl2 extract as the most promising candidate against HAT, showing an IC50 value of 28 μg/mL. On this basis, column chromatography coupled with the NMR spectroscopy of a MarrInc-CH2Cl2 extract led to the isolation and identification of five compounds i.e. 1-α-linolenoyl-2-palmitoyl-3-stearoyl-sn- glycerol (1), 1-linoleoyl-2-palmitoyl-3-stearoyl-sn-glycerol (2), stigmasterol (3), palmitic acid (4), and salvigenin (5). Notably, compounds 3 and 5 were tested on T. brucei, with the latter being five-fold more active than the MarrInc-CH2Cl2 extract (IC50 = 5.41 ± 0.85 and 28 ± 1.4 μg/mL, respectively). Furthermore, the SI for salvigenin was >18.5, showing a preferential effect on target cells compared with the dichloromethane extract (>3.6). Conversely, stigmasterol was found to be inactive. To complete the work, also the more polar MarrInc-EtOH extract was analyzed, giving evidence for the presence of 2″-O-allopyranosyl-cosmosiin (6), verbascoside (7), and samioside (8). Our findings shed light on the phytochemistry of this overlooked species and its antiprotozoal potential, providing evidence for the promising role of flavonoids such as salvigenin for the treatment of protozoal diseases.
Monitoring Hydroxycinnamic Acid Decarboxylation by Lactic Acid Bacteria Using High-Throughput UV-Vis Spectroscopy
Authors: Miyagusuku-Cruzado Gonzalo , García-Cano Israel , Rocha-Mendoza Diana , Jiménez-Flores Rafael , Giusti M. Monica
Published: July 2020

Hydroxycinnamic acid (HCA) decarboxylation by lactic acid bacteria (LAB) results in the production of 4-vinylplenols with great impact on the sensorial characteristics of foods. The determination of LAB decarboxylating capabilities is key for optimal strain selection for food production. The activity of LAB strains from the Ohio State University—Parker Endowed Chair (OSU-PECh) collection potentially capable of synthesizing phenolic acid decarboxylase was evaluated after incubation with HCAs for 36 h at 32 °C. A high-throughput method for monitoring HCAs decarboxylation was developed based on hypsochromic shifts at pH 1.0. Out of 22 strains evaluated, only Enterococcus mundtii, Lactobacillus plantarum and Pediococcus pentosaceus were capable of decarboxylating all p-coumaric, caffeic and ferulic acids. Other strains only decarboxylated p-coumaric and caffeic acid (6), only p-coumaric acid (2) or only caffeic acid (1), while 10 strains did not decarboxylate any HCA. p-Coumaric acid had the highest conversion efficiency, followed by caffeic acid and lastly ferulic acid. Results were confirmed by HPLC-DAD-ESI-MS analyses, showing the conversion of HCAs into their 4-vinylphenol derivatives. This work can help improve the sensory characteristics of HCA-rich foods where fermentation with LAB was used during processing.
Synthesis of Fluorinated 3,6-Dihydropyridines and 2-(Fluoromethyl)pyridines by Electrophilic Fluorination of 1,2-Dihydropyridines with Selectfluor®
Authors: Pikun Nadiia V. , Sobolev Arkadij , Plotniece Aiva , Rucins Martins , Vigante Brigita , Petrova Marina , Muhamadejev Ruslan , Pajuste Karlis , Shermolovich Yuriy G.
Published: July 2020

New fluorinated 3,6-dihydropyridines were obtained by the electrophilic fluorination of 1,2-dihydropyridines with Selectfluor®. These 3-fluoro-3,6-dihydropyridines were easily converted to corresponding pyridines by the elimination of hydrogen fluoride under mild conditions. A new approach to the synthesis of methyl 2-(fluoromethyl)-5-nitro-6-arylnicotinates by the fluorination of 3-fluoro-2-methyl-5-nitro-3,6-dihydropyridines or 1,2-dihydropyridines with Selectfluor® has been developed.
Second-Generation Pharmacological Chaperones: Beyond Inhibitors
Authors: Tran My Lan , Génisson Yves , Ballereau Stéphanie , Dehoux Cécile
Published: July 2020

Protein misfolding induced by missense mutations is the source of hundreds of conformational diseases. The cell quality control may eliminate nascent misfolded proteins, such as enzymes, and a pathological loss-of-function may result from their early degradation. Since the proof of concept in the 2000s, the bioinspired pharmacological chaperone therapy became a relevant low-molecular-weight compound strategy against conformational diseases. The first-generation pharmacological chaperones were competitive inhibitors of mutant enzymes. Counterintuitively, in binding to the active site, these inhibitors stabilize the proper folding of the mutated protein and partially rescue its cellular function. The main limitation of the first-generation pharmacological chaperones lies in the balance between enzyme activity enhancement and inhibition. Recent research efforts were directed towards the development of promising second-generation pharmacological chaperones. These non-inhibitory ligands, targeting previously unknown binding pockets, limit the risk of adverse enzymatic inhibition. Their pharmacophore identification is however challenging and likely requires a massive screening-based approach. This review focuses on second-generation chaperones designed to restore the cellular activity of misfolded enzymes. It intends to highlight, for a selected set of rare inherited metabolic disorders, the strategies implemented to identify and develop these pharmacologically relevant small organic molecules as potential drug candidates.
Screening Risk Assessment of Agricultural Areas under a High Level of Anthropopressure Based on Chemical Indexes and VIS-NIR Spectroscopy
Authors: Klimkowicz-Pawlas Agnieszka , Debaene Guillaume
Published: July 2020

Intensive anthropogenic activity may result in uncontrolled release of various pollutants that ultimately accumulate in soils and may adversely affect ecosystems and human health. Hazard screening, prioritisation and subsequent risk assessment are usually performed on a chemical-by-chemical basis and need expensive and time-consuming methods. Therefore, there is a need to look for fast and reliable methods of risk assessment and contamination prediction in soils. One promising technique in this regard is visible and near infrared (VIS-NIR) spectroscopy. The aim of the study was to evaluate potential environmental risk in soils subjected to high level of anthropopressure using VIS-NIR spectroscopy and to calculate several risk indexes for both individual polycyclic aromatic hydrocarbons (PAHs) and their mixture. Results showed that regarding 16PAH concentration, 78% of soil samples were contaminated. Risk assessment using the most conservative approach based on hazard quotients (HQ) for 10 individual PAHs allowed to conclude that 62% of the study area needs further action. Application of concentration addition or response addition models for 16PAHs mixture gave a more realistic assessment and indicates unacceptable risk in 23% and 55% of soils according to toxic units (TUm) and toxic pressure (TPm) approach. Toxic equivalency quotients (TEQ) were below the safe limit for human health protection in 88% of samples from study region. We present here the first attempt at predicting risk indexes using VIS-NIR spectroscopy. The best results were obtained with binary models. The accuracy of binary model can be ordered as follows: TPm (71.6%) < HI (85.1%) < TUm (87.9%) and TEQ (94.6%). Both chemical indexes and VIS-NIR can be successfully applied for first-tier risk assessment.
Cytotoxic Phenanthrene, Dihydrophenanthrene, and Dihydrostilbene Derivatives and Other Aromatic Compounds from Combretum laxum
Authors: Bisoli Eder , Freire Talita Vilalva , Yoshida Nídia Cristiane , Garcez Walmir Silva , Queiróz Lyara Meira Marinho , Matos Maria de Fátima Cepa , Perdomo Renata Trentin , Garcez Fernanda Rodrigues
Published: July 2020

The chemical investigation of the roots and stems of Combretum laxum yielded a new dihydrostilbene derivative, 4′-hydroxy-3,3′,4-trimethoxy-5-(3,4,5-trimethoxyphenoxy)-bibenzyl (1), two phenanthrenes (2–3), and three dihydrophenanthrenes (4–6), along with one lignan, three triterpenoids, one aurone, one flavone, one naphthoquinone, and two benzoic acid derivatives. Their structures were determined by 1D and 2D nuclear magnetic resonance (NMR) spectroscopic techniques and/or mass spectrometry data. The occurrence of dihydrostilbenoid, phenanthrene and dihydrophenanthrene derivatives is unprecedented in a Combretum species native to the American continent. 2,7-Dihydroxy-4,6-dimethoxyphenanthrene, 2,6-dihydroxy-4,7-dimethoxy-9,10-dihydrophenanthrene and 5-O-methyl apigenin are novel findings in the Combretaceae, as is the isolation of compounds belonging to the chemical classes of aurones and naphthoquinones, while (+)-syringaresinol is reported for the first time in the genus Combretum. Compounds 1–6 were also evaluated for their in vitro cytotoxicity against five human cancer cell lines, and radical-scavenging ability against 1,1-diphenyl-2-picryl-hydrazyl (DPPH). 6-Methoxycoelonin (4) was the most cytotoxic against melanoma cells (IC50 2.59 ± 0.11 µM), with a high selectivity index compared with its toxicity against nontumor mammalian cells (SI 25.1). Callosin (6), despite exhibiting the strongest DPPH-scavenging activity (IC50 17.7 ± 0.3 µM), proved marginally inhibitory to the five cancer cell lines tested, indicating that, at least for these cells, antioxidant potential is unrelated to antiproliferative activity.
Technologies and Formulation Design of Polysaccharide-Based Hydrogels for Drug Delivery
Authors: Auriemma Giulia , Russo Paola , Del Gaudio Pasquale , García-González Carlos A. , Landín Mariana , Aquino Rita Patrizia
Published: July 2020

Polysaccharide-based hydrogel particles (PbHPs) are very promising carriers aiming to control and target the release of drugs with different physico-chemical properties. Such delivery systems can offer benefits through the proper encapsulation of many drugs (non-steroidal and steroidal anti-inflammatory drugs, antibiotics, etc) ensuring their proper release and targeting. This review discusses the different phases involved in the production of PbHPs in pharmaceutical technology, such as droplet formation (SOL phase), sol-gel transition of the droplets (GEL phase) and drying, as well as the different methods available for droplet production with a special focus on prilling technique. In addition, an overview of the various droplet gelation methods with particular emphasis on ionic cross-linking of several polysaccharides enabling the formation of particles with inner highly porous network or nanofibrillar structure is given. Moreover, a detailed survey of the different inner texture, in xerogels, cryogels or aerogels, each with specific arrangement and properties, which can be obtained with different drying methods, is presented. Various case studies are reported to highlight the most appropriate application of such systems in pharmaceutical field. We also describe the challenges to be faced for the breakthrough towards clinic studies and, finally, the market, focusing on the useful approach of safety-by-design (SbD).
The Grapefruit Effect: Interaction between Cytochrome P450 and Coumarin Food Components, Bergamottin, Fraxidin and Osthole. X-ray Crystal Structure and DFT Studies
Authors: Rossi Miriam , Aktar Sandjida , Davis Marissa , Hefter Feuss Emily , Roman-Holba Samara , Wen Kelly , Gahn Christopher , Caruso Francesco
Published: July 2020

Coumarins are plant-derived secondary metabolites. The crystal structure of three coumarins—bergamottin, osthole and fraxidin—are described and we analyze intermolecular interactions and their role in crystal formation. Bergamottin is a furanocoumarin found in citrus plants, which is a strong inhibitor of the principal human metabolizing enzyme, cytochrome P450 3A4 (CYP3A4). The crystal structure determinations of three coumarins give us the geometrical parameters and reveal the parallel-displaced π–π stacking and hydrogen bonding intermolecular interactions used for molecular assembly in the crystal structure. A quite strong (less than 3.4 Å) stacking interaction of bergamottin appears to be a determining feature that distinguishes it from other coumarins studied in this work. Our DFT computational studies on the three natural products of the same coumarin family docked into the active site of CYP3A4 (PDB 4D78) show different behavior for these coumarins at the active site. When the substrate is bergamottin, the importance of π-π stacking and hydrogen bonding, which can anchor the substrate in place, appears fundamental. In contrast, fraxidin and osthole show carbonyl coordination to iron. Our docking calculations show that the bergamottin tendency towards π–π stacking is important and likely influences its interactions with the heme group of CYP3A4.
Switching the Conformation of 3,2′:6′,3″-tpy Domains in 4′-(4-n-Alkyloxyphenyl)-3,2′:6′,3″-Terpyridines
Authors: Rocco Dalila , Prescimone Alessandro , Constable Edwin C. , Housecroft Catherine E.
Published: July 2020

The preparation and characterization of 4′-(4-n-octyloxyphenyl)-3,2′:6′,3″-terpyridine (8) and 4′-(4-n-nonyloxyphenyl)-3,2′:6′,3″-terpyridine (9) are reported. The single crystal structures of 4′-(4-n-hexyloxyphenyl)-3,2′:6′,3″-terpyridine (6), 4′-(4-n-heptyloxyphenyl)-3,2′:6′,3″-terpyridine (7), and compounds 8 and 9 have been determined. The conformation of the 3,2′:6′,3″-tpy unit is trans,trans in 6 and 7, but switches to cis,trans in 8 and 9. This is associated with significant changes in the packing interactions with a more dominant role for van der Waals interactions between adjacent n-alkyloxy chains and C–Hmethylene... π interactions in 8 and 9. The solid-state structures of 6 and 7 with the n-hexyloxy and n-heptyloxy chains feature interwoven sheets of supramolecular assemblies of molecules, with pairs of n-alkyloxy chains threaded through cavities in an adjacent sheet.
Supercritical Fluid Extraction of Celery and Parsley Fruit-Chemical Composition and Antibacterial Activity
Authors: Misic Dusan , Tadic Vanja , Korzeniowska Malgorzata , Nisavic Jakov , Aksentijevic Ksenija , Kuzmanovic Jelena , Zizovic Irena
Published: July 2020

Supercritical fluid extraction as an environmentally friendly technology was applied to isolate biologically active extracts from celery and parsley fruits for potential applications in the food industry. The extractions were performed under mild temperature conditions of 39.85 °C and at pressures of 10 and 30 MPa. The extracts were analyzed regarding their chemical composition, antibacterial activity, and cytotoxic effect. Sedanolide was the dominant component of the celery fruit extracts, comprising more than 70% of the obtained fraction, while the content of apiole in the parsley fruit SC CO2 extracts exceeded 85%. The celery fruit extracts showed strong and moderately strong antibacterial activity against tested Staphylococcus aureus, Bacillus (B.) cereus, B. subtilis, B. circulans, Listeria (L.) greyi, L. seeligeri and L. welshimeri, with minimal inhibitory concentration (MIC) values between 160 and 640 µg/mL, and weak activity against the selected Salmonella isolates with a MIC of 2560 µg/mL. The parsley extract obtained at 10 MPa showed strong and moderately strong antibacterial effects against Bacillus strains with obtained MICs of 160–640 µg/mL, and weak activity against Staphylococcus, Listeria, and Salmonella with a MIC of 2560 µg/mL. Cytotoxicity investigation showed that the extracts with proven antibacterial activity had no cytotoxic effect on rabbit kidney cells at concentrations of up to 640 µg/mL.
Synthesis of Copper and Copper Oxide Nanomaterials by Pulsed Electric Field in Water with Various Electrical Conductivities
Authors: Hamdan Ahmad , Glad Xavier , Cha Min Suk
Published: July 2020

Nanomaterial synthesis is a hot research subject that has been extensively studied in the last two decades. Recently, plasmas in liquid systems have been proposed as an efficient means of synthesizing various types of nanomaterials. The formation processes implicate many physical and chemical phenomena that take place at the electrode surface, as well as in the plasma volume, which renders it difficult to fully understand the underlying mechanisms. In this study, we assess the effect of electric field on nanomaterial synthesis in a system composed of two copper electrodes immersed in water, in the absence of an electrical discharge. The obtained results indicate that various nanostructures, including copper nanoparticles, copper oxide nanowires, and/or hollow nanoparticles, may be produced, depending on the electrical conductivity of the solution (adjusted by adding highly diluted HCl to deionized water). The materials synthesized herein are collected and characterized, and a formation mechanism is proposed. Overall, our results provide insight into the physical and chemical phenomena underlying nanomaterial synthesis in plasmas in liquid.
Endothelial Cell Targeting by cRGD-Functionalized Polymeric Nanoparticles under Static and Flow Conditions
Authors: Martínez-Jothar Lucía , Barendrecht Arjan D. , de Graaff Anko M. , Oliveira Sabrina , van Nostrum Cornelus F. , Schiffelers Raymond M. , Hennink Wim E. , Fens Marcel H. A. M.
Published: July 2020

Since αvβ3 integrin is a key component of angiogenesis in health and disease, Arg-Gly-Asp (RGD) peptide-functionalized nanocarriers have been investigated as vehicles for targeted delivery of drugs to the αvβ3 integrin-overexpressing neovasculature of tumors. In this work, PEGylated nanoparticles (NPs) based on poly(lactic-co-glycolic acid) (PLGA) functionalized with cyclic-RGD (cRGD), were evaluated as nanocarriers for the targeting of angiogenic endothelium. For this purpose, NPs (~300 nm) functionalized with cRGD with different surface densities were prepared by maleimide-thiol chemistry and their interactions with human umbilical vein endothelial cells (HUVECs) were evaluated under different conditions using flow cytometry and microscopy. The cell association of cRGD-NPs under static conditions was time-, concentration- and cRGD density-dependent. The interactions between HUVECs and cRGD-NPs dispersed in cell culture medium under flow conditions were also time- and cRGD density-dependent. When washed red blood cells (RBCs) were added to the medium, a 3 to 8-fold increase in NPs association to HUVECs was observed. Moreover, experiments conducted under flow in the presence of RBC at physiologic hematocrit and shear rate, are a step forward in the prediction of in vivo cell–particle association. This approach has the potential to assist development and high-throughput screening of new endothelium-targeted nanocarriers.
Magnesium Sulfate-Rich Natural Mineral Waters in the Treatment of Functional Constipation–A Review
Authors: Dupont Christophe , Hébert Guillaume
Published: July 2020

Functional constipation (FC) is a chronic constipation for which no physiological, anatomical or iatrogenic origin can be evidenced. This condition has a high impact on a patient’s quality of life and healthcare costs. Since FC is frequently associated with low physical activity and a diet low in fiber and/or water, first-line recommendations focus on sufficient activity, and sufficient fiber and water intake. In case of inefficacy of these measures, numerous drug treatments are available, either over the counter or on prescription. Magnesium sulfate has a long history in the treatment of FC, and magnesium sulfate-rich mineral waters have been used for centuries for their laxative properties. The laxative effect of magnesium and sulfate has since been widely demonstrated. Nevertheless, it appears that no clinical studies aiming at demonstrating their efficacy in FC had been conducted before the 21st century. In this paper, we reviewed the clinical data reporting the efficacy of magnesium sulfate-rich natural mineral waters. In view of their reported efficacy and safety, magnesium sulfate-rich natural mineral waters may represent a natural treatment for FC.