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Molecules, Volume 24, Issue 18 (September-2 2019)

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Open AccessArticle
Purification, Characterization, and Application for Preparation of Antioxidant Peptides of Extracellular Protease from Pseudoalteromonas sp. H2
Molecules 2019, 24(18), 3373; https://doi.org/10.3390/molecules24183373 (registering DOI) - 16 Sep 2019
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Abstract
The study reported on the isolation of a metalloprotease named EH2 from Pseudoalteromonas sp. H2. EH2 maintained more than 80% activity over a wide pH range of 5–10, and the stability was also nearly independent of pH. Over 65% activity was detected at [...] Read more.
The study reported on the isolation of a metalloprotease named EH2 from Pseudoalteromonas sp. H2. EH2 maintained more than 80% activity over a wide pH range of 5–10, and the stability was also nearly independent of pH. Over 65% activity was detected at a wide temperature range of 20–70 °C. The high stability of the protease in the presence of different surfactants and oxidizing agents was also observed. Moreover, we also investigated the antioxidant activities of the hydrolysates generated from porcine and salmon skin collagen by EH2. The results showed that salmon skin collagen hydrolysates demonstrated higher DPPH (1,1-diphenyl-2-picrylhydrazyl) (42.88% ± 1.85) and hydroxyl radical (61.83% ± 3.05) scavenging activity than porcine skin collagen. For oxygen radical absorbance capacity, the hydrolysates from porcine skin collagen had higher efficiency (7.72 ± 0.13 μmol·TE/μmol). Even 1 nM mixed peptides could effectively reduce the levels of intracellular reactive oxygen species. The two types of substrates exerted the best antioxidant activity when hydrolyzed for 3 h. The hydrolysis time and type of substrate exerted important effects on the antioxidant properties of hydrolysates. The hydrolyzed peptides from meat collagens by proteases have good antioxidant activity, which may have implications for the potential application of marine proteases in the biocatalysis industry. Full article
(This article belongs to the Section Chemical Biology)
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Open AccessReview
Autophagy Modulation as a Treatment of Amyloid Diseases
Molecules 2019, 24(18), 3372; https://doi.org/10.3390/molecules24183372 (registering DOI) - 16 Sep 2019
Viewed by 131
Abstract
Amyloids are fibrous proteins aggregated into toxic forms that are implicated in several chronic disorders. More than 30 diseases show deposition of fibrous amyloid proteins associated with cell loss and degeneration in the affected tissues. Evidence demonstrates that amyloid diseases result from protein [...] Read more.
Amyloids are fibrous proteins aggregated into toxic forms that are implicated in several chronic disorders. More than 30 diseases show deposition of fibrous amyloid proteins associated with cell loss and degeneration in the affected tissues. Evidence demonstrates that amyloid diseases result from protein aggregation or impaired amyloid clearance, but the connection between amyloid accumulation and tissue degeneration is not clear. Common examples of amyloid diseases are Alzheimer’s disease (AD), Parkinson’s disease (PD) and tauopathies, which are the most common forms of neurodegenerative diseases, as well as polyglutamine disorders and certain peripheral metabolic diseases. In these diseases, increased accumulation of toxic amyloid proteins is suspected to be one of the main causative factors in the disease pathogenesis. It is therefore important to more clearly understand how these toxic amyloid proteins accumulate as this will aide in the development of more effective preventive and therapeutic strategies. Protein homeostasis, or proteostasis, is maintained by multiple cellular pathways—including protein synthesis, quality control, and clearance—which are collectively responsible for preventing protein misfolding or aggregation. Modulating protein degradation is a very complex but attractive treatment strategy used to remove amyloid and improve cell survival. This review will focus on autophagy, an important clearance pathway of amyloid proteins, and strategies for using it as a potential therapeutic target for amyloid diseases. The physiological role of autophagy in cells, pathways for its modulation, its connection with apoptosis, cell models and caveats in developing autophagy as a treatment and as a biomarker is discussed. Full article
(This article belongs to the Special Issue Amyloid Inhibitors and Modulators)
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Open AccessArticle
Bifunctional Bioactive Polymer Surfaces with Micrometer and Submicrometer-sized Structure: The Effects of Structure Spacing and Elastic Modulus on Bioactivity
Molecules 2019, 24(18), 3371; https://doi.org/10.3390/molecules24183371 (registering DOI) - 16 Sep 2019
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Abstract
This study presents a comparison of two types of bifunctional structured surface that were made from the same polymer –– an antimicrobial polycation (a synthetic mimic of an antimicrobial peptide, SMAMP) and a protein-repellent polyzwitterion (poly(sulfobetaines), PSB). The first type of bifunctional surface [...] Read more.
This study presents a comparison of two types of bifunctional structured surface that were made from the same polymer –– an antimicrobial polycation (a synthetic mimic of an antimicrobial peptide, SMAMP) and a protein-repellent polyzwitterion (poly(sulfobetaines), PSB). The first type of bifunctional surface was fabricated by a colloidal lithography (CL) based process where the two polymers were immobilized sequentially onto pre-structured surfaces with a chemical contrast (gold on silicon). This enabled site-selective covalent attachment. The CL materials had a spacing ranging from 200 nm to 2 µm. The second type of structured surface (spacing: 1 – 8.5 µm) was fabricated using a microcontact printing (µCP) process where SMAMP patches were printed onto a PSB network, so that 3D surface features were obtained. The thus obtained materials were studied by quantitative nanomechanical measurements using atomic force microscopy (QNM-AFM). The different architectures led to different local elastic moduli at the polymer-air interface, where the CL surfaces were much stiffer (Derjaguin-Muller-Toporov (DMT) modulus = 20 ± 0.8 GPa) compared to the structured 3D networks obtained by µCP (DMT modulus = 42 ± 1.1 MPa). The effects of the surface topology and stiffness on the antimicrobial activity against Escherichia coli, the protein repellency (using fibrinogen), and the compatibility with human gingival mucosal keratinocytes were investigated. The softer 3D µCP surfaces had simultaneous antimicrobial activity, protein repellency, and cell compatibility at all spacings. For the stiffer CL surfaces, quantitative simultaneous antimicrobial activity and protein repellency was not obtained. However, the cell compatibility could be maintained at all spacings. The optimum spacing for the CL materials was in the range of 500 nm–1 µm, with significantly reduced antimicrobial activity at 2 µm spacing. Thus, the soft polymer network obtained by µCP could be more easily optimized than the stiff CL surface, and had a broader topology range of optimal or near-optimal bioactivity. Full article
(This article belongs to the Special Issue Chemical Surface Functionalization)
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Open AccessArticle
Intermolecular Non-Covalent Carbon-Bonding Interactions with Methyl Groups: A CSD, PDB and DFT Study
Molecules 2019, 24(18), 3370; https://doi.org/10.3390/molecules24183370 (registering DOI) - 16 Sep 2019
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Abstract
A systematic evaluation of the CSD and the PDB in conjunction with DFT calculations reveal that non-covalent Carbon-bonding interactions with X–CH3 can be weakly directional in the solid state (P ≤ 1.5) when X = N or O. This is comparable [...] Read more.
A systematic evaluation of the CSD and the PDB in conjunction with DFT calculations reveal that non-covalent Carbon-bonding interactions with X–CH3 can be weakly directional in the solid state (P ≤ 1.5) when X = N or O. This is comparable to very weak CH hydrogen bonding interactions and is in line with the weak interaction energies calculated (≤ –1.5 kcal·mol−1) of typical charge neutral adducts such as [Me3N-CH3···OH2] (2a). The interaction energy is enhanced to ≤–5 kcal·mol−1 when X is more electron withdrawing such as in [O2N-CH3··O=Cdme] (20b) and to ≤18 kcal·mol−1 in cationic species like [Me3O+-CH3···OH2]+ (8a). Full article
(This article belongs to the Special Issue Tetrel Bonds)
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Open AccessArticle
Investigation of Metal-Organic Framework-5 (MOF-5) as an Antitumor Drug Oridonin Sustained Release Carrier
Molecules 2019, 24(18), 3369; https://doi.org/10.3390/molecules24183369 (registering DOI) - 16 Sep 2019
Viewed by 152
Abstract
Oridonin (ORI) is a natural active ingredient with strong anticancer activity. But its clinical use is restricted due to its poor water solubility, short half-life, and low bioavailability. The aim of this study is to utilize the metal organic framework material MOF-5 to [...] Read more.
Oridonin (ORI) is a natural active ingredient with strong anticancer activity. But its clinical use is restricted due to its poor water solubility, short half-life, and low bioavailability. The aim of this study is to utilize the metal organic framework material MOF-5 to load ORI in order to improve its release characteristics and bioavailability. Herein, MOF-5 was synthesized by the solvothermal method and direct addition method, and characterized by Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Fourier Transform Infrared Spectrometer (FTIR), Thermogravimetric Analysis (TG), Brunauer–Emmett–Teller (BET), and Dynamic Light Scattering (DLS), respectively. MOF-5 prepared by the optimal synthesis method was selected for drug-loading and in vitro release experiments. HepG2 cells were model cells. MTT assay, 4′,6-diamidino-2-phenylindole (DAPI) staining and Annexin V/PI assay were used to detect the biological safety of blank carriers and the anticancer activity of drug-loaded materials. The results showed that nano-MOF-5 prepared by the direct addition method had complete structure, uniform size and good biocompatibility, and was suitable as an ORI carrier. The drug loading of [email protected] was 52.86% ± 0.59%. The sustained release effect was reliable, and the cumulative release rate was about 87% in 60 h. [email protected] had significant cytotoxicity (IC50:22.99 μg/mL) and apoptosis effect on HepG2 cells. [email protected] is hopeful to become a new anticancer sustained release preparation. MOF-5 has significant potential as a drug carrier material. Full article
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Open AccessArticle
Identification of Resveratrol as Bioactive Compound of Propolis from Western Romania and Characterization of Phenolic Profile and Antioxidant Activity of Ethanolic Extracts
Molecules 2019, 24(18), 3368; https://doi.org/10.3390/molecules24183368 (registering DOI) - 16 Sep 2019
Viewed by 145
Abstract
The present study aimed to assess the phenolic content of eight ethanolic propolis samples (P1–P8) harvested from different regions of Western Romania and their antioxidant activity. The mean value of total phenolic content was 214 ± 48 mg gallic acid equivalents (GAE)/g propolis. [...] Read more.
The present study aimed to assess the phenolic content of eight ethanolic propolis samples (P1–P8) harvested from different regions of Western Romania and their antioxidant activity. The mean value of total phenolic content was 214 ± 48 mg gallic acid equivalents (GAE)/g propolis. All extracts contained kaempferol (514.02 ± 114.80 μg/mL), quercetin (124.64 ± 95.86 μg/mL), rosmarinic acid (58.03 ± 20.08 μg/mL), and resveratrol (48.59 ± 59.52 μg/mL) assessed by LC-MS. The antioxidant activity was evaluated using 2 methods: (i) DPPH (2,2-diphenyl-1-picrylhydrazyl) assay using ascorbic acid as standard antioxidant and (ii) FOX (Ferrous iron xylenol orange OXidation) assay using catalase as hydrogen peroxide (H2O2) scavenger. The DPPH radical scavenging activity was determined for all samples applied in 6 concentrations (10, 5, 3, 1.5, 0.5 and 0.3 mg/mL). IC50 varied from 0.0700 to 0.9320 mg/mL (IC50 of ascorbic acid = 0.0757 mg/mL). The % of H2O2 inhibition in FOX assay was assessed for P1, P2, P3, P4 and P8 applied in 2 concentrations (5 and 0.5 mg/mL). A significant H2O2% inhibition was obtained for these samples for the lowest concentration. We firstly report the presence of resveratrol as bioactive compound in Western Romanian propolis. The principal component analysis revealed clustering of the propolis samples according to the polyphenolic profile similarity. Full article
(This article belongs to the Special Issue Biological Activities of Honeybee Products)
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Open AccessFeature PaperArticle
Improving Interlaminar Fracture Toughness and Impact Performance of Carbon Fiber/Epoxy Laminated Composite by Using Thermoplastic Fibers
Molecules 2019, 24(18), 3367; https://doi.org/10.3390/molecules24183367 (registering DOI) - 16 Sep 2019
Viewed by 118
Abstract
The effects of thermoplastic polyimide (PI) and polypropylene (PP) fibers and areal density of toughened layer on interlaminar fracture toughness and impact performance of carbon fiber/epoxy (CF/EP) laminated composites were studied. Mode I interlaminar fracture toughness (GIC) was analyzed via double [...] Read more.
The effects of thermoplastic polyimide (PI) and polypropylene (PP) fibers and areal density of toughened layer on interlaminar fracture toughness and impact performance of carbon fiber/epoxy (CF/EP) laminated composites were studied. Mode I interlaminar fracture toughness (GIC) was analyzed via double cantilever beam (DCB) tests. When comparing for the toughener type, PI played a positive role in enhancing the mode-I fracture toughness, while PP was not effective due to the less fiber bridge formed during composite curing. The toughening effects of areal density of PI were further investigated by end notched flexure (ENF) testing and low velocity impact testing to better understand the toughening mechanisms. The results revealed that the toughening effect reached its best effectiveness when the areal density of toughened layer was 30 g/m2. Compared with the control group, GIC and GIIC of CF/EP laminated composite were increased by 98.49% and 84.07%, and Fmax and Ee were enhanced by 92.38% and 299.08% under low velocity impact. There is no obvious delamination phenomenon on the surface of laminates after low velocity impact, indicating the improved interlaminar and impact performance of laminated composite. Full article
(This article belongs to the Special Issue Fibre Reinforced Composites: Interfacial Modifications and Property)
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Open AccessArticle
Effect of Nanocrystallization of Anthocyanins Extracted from Two Types of Red-Fleshed Apple Varieties on Its Stability and Antioxidant Activity
Molecules 2019, 24(18), 3366; https://doi.org/10.3390/molecules24183366 (registering DOI) - 16 Sep 2019
Viewed by 150
Abstract
Red-fleshed apple (Malus sieversii f. neidzwetzkyana (Dieck) Langenf) has attracted more and more attention due to its enriched anthocyanins and high antioxidant activity. In this study we extracted total anthocyanins and phenols from two types of red-fleshed apples—Xinjing No.4 (XJ4) and Red [...] Read more.
Red-fleshed apple (Malus sieversii f. neidzwetzkyana (Dieck) Langenf) has attracted more and more attention due to its enriched anthocyanins and high antioxidant activity. In this study we extracted total anthocyanins and phenols from two types of red-fleshed apples—Xinjing No.4 (XJ4) and Red Laiyang (RL)—to study the stability and antioxidant activity of anthocyanins after encapsulation onto Corn Starch Nanoparticles (CSNPs). The results indicated the anthocyanins and total phenol levels of XJ4 were 2.96 and 2.25 times higher than those of RL respectively. The anthocyanin concentration and loading time had a significant effect on CSNPs encapsulation, and XJ4 anthocyanins always showed significantly higher loading capacity than RL. After encapsulation, the morphology of RL-CSNPs and XJ4-CSNPs was still spherical with a smooth surface as CSNPs, but the particle size increased compared to CSNPs especially for RL-CSNPs. Different stress treatments including UV light, pH, temperature, and salinity suggested that XJ4-CSNPs exhibited consistently higher stability than RL-CSNPs. A significantly enhanced free radical scavenging rate under stress conditions was observed, and XJ4-CSNPs had stronger antioxidant activity than RL-CSNPs. Furthermore, XJ4-CSNPs exhibited a slower released rate than RL-CSNPs in simulated gastric (pH 2.0) and intestinal (pH 7.0) environments. Our research suggests that nanocrystallization of anthocyanins is an effective method to keep the anthocyanin ingredients intact and active while maintaining a slow release rate. Compared to RL, encapsulation of XJ4 anthocyanins has more advantages, which might be caused by the significant differences in the metabolites of XJ4. These findings give an insight into understanding the role of nanocrystallization using CSNPs in enhancing the antioxidant ability of anthocyanins from different types of red-fleshed apples, and provide theoretical foundations for red-fleshed apple anthocyanin application. Full article
(This article belongs to the Special Issue Antioxidants Chemistry and Applications)
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Open AccessArticle
Development and Validation of a Virtual Gelatin Model Using Molecular Modeling Computational Tools
Molecules 2019, 24(18), 3365; https://doi.org/10.3390/molecules24183365 (registering DOI) - 16 Sep 2019
Viewed by 148
Abstract
To successfully design and optimize the application of hydrogel matrices one has to effectively combine computational design tools with experimental methods. In this context, one of the most promising techniques is molecular modeling, which requires however accurate molecular models representing the investigated material. [...] Read more.
To successfully design and optimize the application of hydrogel matrices one has to effectively combine computational design tools with experimental methods. In this context, one of the most promising techniques is molecular modeling, which requires however accurate molecular models representing the investigated material. Although this method has been successfully used over the years for predicting the properties of polymers, its application to biopolymers, including gelatin, is limited. In this paper we provide a method for creating an atomistic representation of gelatin based on the modified FASTA codes of natural collagen. We show that the model created in this manner reproduces known experimental values of gelatin properties like density, glass-rubber transition temperature, WAXS profile and isobaric thermal expansion coefficient. We also present that molecular dynamics using the INTERFACE force field provides enough accuracy to track changes of density, fractional free volume and Hansen solubility coefficient over a narrow temperature regime (273–318 K) with 1 K accuracy. Thus we depict that using molecular dynamics one can predict properties of gelatin biopolymer as an efficient matrix for immobilization of various bioactive compounds, including enzymes. Full article
(This article belongs to the Special Issue Gelatin: Chemistry, Characterization, Application)
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Open AccessArticle
Structural Characterization and Antioxidant Activity of Polysaccharides from Athyrium multidentatum (Doll.) Ching in d-Galactose-Induced Aging Mice via PI3K/AKT Pathway
Molecules 2019, 24(18), 3364; https://doi.org/10.3390/molecules24183364 (registering DOI) - 16 Sep 2019
Viewed by 143
Abstract
The purpose of this study was to characterize the polysaccharides from Athyrium multidentatum (Doll.) Ching (AMC) rhizome and explore the protective mechanism against d-galactose-induced oxidative stress in aging mice. Methods: A series of experiments, including molecular weight, monosaccharide composition, Fourier transform infrared [...] Read more.
The purpose of this study was to characterize the polysaccharides from Athyrium multidentatum (Doll.) Ching (AMC) rhizome and explore the protective mechanism against d-galactose-induced oxidative stress in aging mice. Methods: A series of experiments, including molecular weight, monosaccharide composition, Fourier transform infrared (FT-IR) spectroscopy, and 1H nuclear magnetic resonance (1H NMR) spectroscopy were carried out to characterize AMC polysaccharides. The mechanism was investigated exploring d-galactose-induced aging mouse model. Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) and western blotting assays were performed to assess the gene and protein expression in liver. Key findings: Our results showed that AMC polysaccharides were mainly composed of mannose (Man), rhamnose (Rha), glucuronic acid (Glc A), glucose (Glc), galactose (Gal), arabinose (Ara), and fucose (Fuc) in a molar ratio of 0.077:0.088:0.09:1:0.375:0.354:0.04 with a molecular weight of 33203 Da (Mw). AMC polysaccharides strikingly reversed d-galactose-induced changes in mice, including upregulated phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor-erythroid 2-related factor 2 (Nrf2), forkhead box O3a (FOXO3a), and hemeoxygenase-1 (HO-1) mRNA expression, raised Bcl-2/Bax ratio, downregulated caspase-3 mRNA expression, enhanced Akt, phosphorylation of Akt (p-Akt), Nrf2 and HO-1 protein expression, decreased caspase-3, and Bax protein expression. Conclusion: AMC polysaccharides attenuated d-galactose-induced oxidative stress and cell apoptosis by activating the PI3K/AKT pathway, which might in part contributed to their anti-aging activity. Full article
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Open AccessArticle
Neutral Lipid Content in Lipid Droplets: Potential Biomarker of Cordycepin Accumulation in Cordycepin-Producing Fungi
Molecules 2019, 24(18), 3363; https://doi.org/10.3390/molecules24183363 (registering DOI) - 16 Sep 2019
Viewed by 119
Abstract
To clarify the relationship between neutral lipid content and cordycepin accumulation in Cordyceps militaris, mutants were generated from mixed spores of two C. militaris strains with varying cordycepin-producing capacities. Fifteen stable mutants producing from 0.001 to 2.363 mg/mL cordycepin were finally selected. [...] Read more.
To clarify the relationship between neutral lipid content and cordycepin accumulation in Cordyceps militaris, mutants were generated from mixed spores of two C. militaris strains with varying cordycepin-producing capacities. Fifteen stable mutants producing from 0.001 to 2.363 mg/mL cordycepin were finally selected. The relative fluorescence intensities of the 15 mutants, two C. militaris strains and an Aspergillus nidulans strain at different concentrations of lyophilized mycelium powder were then investigated using the Nile red method. The mutant CM1-1-1 with the highest relative fluorescence intensity among the eighteen strains was selected for optimizing the Nile red method. Relative fluorescence intensity was linearly correlated with cordycepin concentration in liquid broth (R2 = 0.9514) and in lyophilized mycelium powder (R2 = 0.9378) for the 18 cordycepin-producing strains under identical culture conditions and with cordycepin concentration in liquid broth (R2 = 0.9727) and in lyophilized mycelium powder (R2 = 0.9613) for CM1-1-1 under eight different sets of conditions. In addition, the cordycepin content in lyophilized mycelium powder measured by the Nile red method was linearly correlated with that determined by an HPLC method (R2 = 0.9627). In conclusion, neutral lipids in lipid droplets are required during cordycepin accumulation; these neutral lipids are potential biomarkers of cordycepin biosynthesis. Full article
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Open AccessTechnical Note
A High Throughput Apoptosis Assay using 3D Cultured Cells
Molecules 2019, 24(18), 3362; https://doi.org/10.3390/molecules24183362 - 16 Sep 2019
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Abstract
A high throughput apoptosis assay using 3D cultured cells was developed with a micropillar/microwell chip platform. Live cell apoptosis assays based on fluorescence detection have been useful in high content screening. To check the autofluorescence of drugs, controls (no caspase-3/7 reagent in the [...] Read more.
A high throughput apoptosis assay using 3D cultured cells was developed with a micropillar/microwell chip platform. Live cell apoptosis assays based on fluorescence detection have been useful in high content screening. To check the autofluorescence of drugs, controls (no caspase-3/7 reagent in the assay) for the drugs are necessary which require twice the test space. Thus, a high throughput capability and highly miniaturized format for reducing reagent usage are necessary in live cell apoptosis assays. Especially, the expensive caspase-3/7 reagent should be reduced in a high throughput screening system. To solve this issue, we developed a miniaturized apoptosis assay using micropillar/microwell chips for which we tested seventy drugs (six replicates) per chip and reduced the assay volume to 1 µL. This reduced assay volume can decrease the assay costs compared to the 10–40 µL assay volumes used in 384 well plates. In our experiments, among the seventy drugs, four drugs (Cediranib, Cabozatinib, Panobinostat, and Carfilzomib) induced cell death by apoptosis. Those results were confirmed with western blot assays and proved that the chip platform could be used to identify high potency apoptosis-inducing drugs in 3D cultured cells with alginate. Full article
(This article belongs to the Special Issue High Throughput Screening II)
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Open AccessCommunication
A Novel One-Dimensional Porphyrin-Based Covalent Organic Framework
Molecules 2019, 24(18), 3361; https://doi.org/10.3390/molecules24183361 - 16 Sep 2019
Viewed by 126
Abstract
A novel one-dimensional covalent organic framework (COF-K) was firstly designed and synthesized through a Schiff-based reaction from a porphyrin building block and a nonlinear right-angle building block. The COF-K exhibited high BET surface area and narrow pore size of 1.25 nm and gave [...] Read more.
A novel one-dimensional covalent organic framework (COF-K) was firstly designed and synthesized through a Schiff-based reaction from a porphyrin building block and a nonlinear right-angle building block. The COF-K exhibited high BET surface area and narrow pore size of 1.25 nm and gave a CO2 adsorption capacity of 89 mg g−1 at 273K and 1bar. Full article
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Open AccessArticle
Comparison of the Interactions of Different Growth Factors and Glycosaminoglycans
Molecules 2019, 24(18), 3360; https://doi.org/10.3390/molecules24183360 - 16 Sep 2019
Viewed by 129
Abstract
Most growth factors are naturally occurring proteins, which are signaling molecules implicated in cellular multiple functions such as proliferation, migration and differentiation under patho/physiological conditions by interacting with cell surface receptors and other ligands in the extracellular microenvironment. Many of the growth factors [...] Read more.
Most growth factors are naturally occurring proteins, which are signaling molecules implicated in cellular multiple functions such as proliferation, migration and differentiation under patho/physiological conditions by interacting with cell surface receptors and other ligands in the extracellular microenvironment. Many of the growth factors are heparin-binding proteins (HBPs) that have a high affinity for cell surface heparan sulfate proteoglycans (HSPG). In the present study, we report the binding kinetics and affinity of heparin interacting with different growth factors, including fibroblast growth factor (FGF) 2,7,10, hepatocyte growth factor (HGF) and transforming growth factor (TGF β-1), using a heparin chip. Surface plasmon resonance studies revealed that all the tested growth factors bind to heparin with high affinity (with KD ranging from ~0.1 to 59 nM) and all the interactions are oligosaccharide size dependent except those involving TGF β-1. These heparin-binding growth factors also interact with other glycosaminoglycans (GAGs), as well as various chemically modified heparins. Other GAGs, including heparan sulfate, chondroitin sulfates A, B, C, D, E and keratan sulfate, showed different inhibition activities for the growth factor-heparin interactions. FGF2, FGF7, FGF10 and HGF bind heparin but the 2-O-sulfo and 6-O-sulfo groups on heparin have less impact on these interactions than do the N-sulfo groups. All the three sulfo groups (N-, 2-O and 6-O) on heparin are important for TGFβ-1-heparin interaction. Full article
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Open AccessArticle
Improved Antioxidant, Anti-inflammatory, and Anti-adipogenic Properties of Hydroponic Ginseng Fermented by Leuconostoc mesenteroides KCCM 12010P
Molecules 2019, 24(18), 3359; https://doi.org/10.3390/molecules24183359 - 16 Sep 2019
Viewed by 130
Abstract
Hydroponic ginseng (HPG) has been known to have various bio-functionalities, including an antioxidant effect. Recently, fermentation by lactic acid bacteria has been studied to enhance bio-functional activities in plants by biologically converting their chemical compounds. HPG roots and shoots were fermented with Leuconostoc [...] Read more.
Hydroponic ginseng (HPG) has been known to have various bio-functionalities, including an antioxidant effect. Recently, fermentation by lactic acid bacteria has been studied to enhance bio-functional activities in plants by biologically converting their chemical compounds. HPG roots and shoots were fermented with Leuconostoc mesenteroides KCCM 12010P isolated from kimchi. The total phenolic compounds, antioxidant, anti-inflammatory, and anti-adipogenic effects of these fermented samples were evaluated in comparison with non-fermented samples (control). During 24 h fermentation of HPG roots and shoots, the viable number of cells increased to 7.50 Log colony forming unit (CFU)/mL. Total phenolic and flavonoid contents of the fermented HPG roots increased by 107.19% and 645.59%, respectively, compared to non-fermented HPG roots. The antioxidant activity of fermented HPG, as assessed by 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), β-carotene-linoleic, and ferric reducing antioxidant power (FRAP) assay, was also significantly enhanced. In an anti-inflammatory effect of lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, the nitric oxide content and the expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) decreased when treated with fermented samples. Simultaneously, lipid accumulation in 3T3-L1 adipocyte was reduced when treated with fermented HPG. Fermentation by L. mesenteroides showed improved antioxidant, anti-inflammatory and anti-adipogenic HPG effects. These results show that fermented HPG has potential for applications in the functional food industry. Full article
(This article belongs to the Special Issue Current Trends in Ginseng Research)
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Open AccessArticle
Layered Extraction and Adsorption Performance of Extracellular Polymeric Substances from Activated Sludge in the Enhanced Biological Phosphorus Removal Process
Molecules 2019, 24(18), 3358; https://doi.org/10.3390/molecules24183358 - 16 Sep 2019
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Abstract
A large amount of phosphorus was found in the extracellular polymeric substances (EPS) of activated sludge used in enhanced biological phosphorus removal (EBPR), so the role of EPS and extracellular phosphorus in EBPR should not be neglected. The composition and properties of tightly [...] Read more.
A large amount of phosphorus was found in the extracellular polymeric substances (EPS) of activated sludge used in enhanced biological phosphorus removal (EBPR), so the role of EPS and extracellular phosphorus in EBPR should not be neglected. The composition and properties of tightly bound EPS (TB-EPS) and loosely bound EPS (LB-EPS) were significantly different, and it was necessary to study the adsorption performance of EPS through the fractionating of activated sludge into LB-EPS, TB-EPS and microbial cells. In this study, the adsorption performance of LB-EPS and TB-EPS for phosphate was explored by extracting LB-EPS and TB-EPS via sonication and cation exchange resin (CER), respectively. The results indicated that the sonication-CER method was an efficient and reliable extraction method for EPS with a synergistic effect. The performance of EPS in the adsorption/complexing of phosphate was excellent because of its abundant functional groups. Specifically, the type and content of metal elements and functional groups in TB-EPS were much greater than those in LB-EPS, which led to the key role of TB-EPS in the adsorption/complexing of phosphate. Finally, a metabolic model for EBPR with consideration of the adsorption performance of LB-EPS and TB-EPS was proposed. Full article
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Open AccessArticle
Structural Insights into Influence of Isomerism on Properties of Open Shell Cobalt Coordination System
Molecules 2019, 24(18), 3357; https://doi.org/10.3390/molecules24183357 - 16 Sep 2019
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Abstract
The two coordination compounds of cobalt were designed and synthesized. The substrates were carefully selected to allow gentle tuning of the molecular structure of the designed compounds. The crystal, molecular and supramolecular structure of studied compounds has been determined and discussed. The spectroscopic [...] Read more.
The two coordination compounds of cobalt were designed and synthesized. The substrates were carefully selected to allow gentle tuning of the molecular structure of the designed compounds. The crystal, molecular and supramolecular structure of studied compounds has been determined and discussed. The spectroscopic and thermal properties of designed coordination compounds have been studied and their application as precursors for the synthesis of cobalt oxide nanoparticles has been demonstrated. It was proven that not only are parameters of conversion of the precursor to nanoparticles important, but also small changes in molecular structure can considerably affect the size of formed particles. For unambiguous determination of the influence of compounds structure on their UV-Vis radiation absorption, density functional theory and time-dependent density functions theory calculations have been performed. The complexity of the correct ab-initio reflection of the open shell molecular system was outlined and discussed. The results obtained from density functional theory (DFT) calculations have been also employed for discussion of the bonding properties. Full article
(This article belongs to the Section Inorganic Chemistry)
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Improved Production and In Situ Recovery of Sesquiterpene (+)-Zizaene from Metabolically-Engineered E. coli
Molecules 2019, 24(18), 3356; https://doi.org/10.3390/molecules24183356 - 15 Sep 2019
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Abstract
The sesquiterpene (+)-zizaene is the direct precursor of khusimol, the main fragrant compound of the vetiver essential oil from Chrysopogon zizanioides and used in nearly 20% of men’s fine perfumery. The biotechnological production of such fragrant sesquiterpenes is a promising alternative towards sustainability; [...] Read more.
The sesquiterpene (+)-zizaene is the direct precursor of khusimol, the main fragrant compound of the vetiver essential oil from Chrysopogon zizanioides and used in nearly 20% of men’s fine perfumery. The biotechnological production of such fragrant sesquiterpenes is a promising alternative towards sustainability; nevertheless, product recovery from fermentation is one of the main constraints. In an effort to improve the (+)-zizaene recovery from a metabolically-engineered Escherichia coli, we developed an integrated bioprocess by coupling fermentation and (+)-zizaene recovery using adsorber extractants. Initially, (+)-zizaene volatilization was confirmed from cultivations with no extractants but application of liquid–liquid phase partitioning cultivation (LLPPC) improved (+)-zizaene recovery nearly 4-fold. Furthermore, solid–liquid phase partitioning cultivation (SLPPC) was evaluated by screening polymeric adsorbers, where Diaion HP20 reached the highest recovery. Bioprocess was scaled up to 2 L bioreactors and in situ recovery configurations integrated to fermentation were evaluated. External recovery configuration was performed with an expanded bed adsorption column and improved (+)-zizaene titers 2.5-fold higher than LLPPC. Moreover, internal recovery configuration (IRC) further enhanced the (+)-zizaene titers 2.2-fold, whereas adsorption velocity was determined as critical parameter for recovery efficiency. Consequently, IRC improved the (+)-zizaene titer 8.4-fold and productivity 3-fold from our last report, achieving a (+)-zizaene titer of 211.13 mg L−1 and productivity of 3.2 mg L−1 h−1. This study provides further knowledge for integration of terpene bioprocesses by in situ product recovery, which could be applied for many terpene studies towards the industrialization of fragrant molecules. Full article
(This article belongs to the Section Green Chemistry)
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Chemical Composition, In Vitro Antioxidant Potential, and Antimicrobial Activities of Essential Oils and Hydrosols from Native American Muscadine Grapes
Molecules 2019, 24(18), 3355; https://doi.org/10.3390/molecules24183355 - 15 Sep 2019
Viewed by 269
Abstract
Essential oils and hydrosols of two cultivars of muscadine grapes (Muscadinia rotundifolia (Michx.) Small.) were obtained by hydro-distillation of flowers and berry skins. Twenty-three volatile compounds were identified in essential oils from the muscadine flowers, and twenty volatiles in their corresponding hydrosols. [...] Read more.
Essential oils and hydrosols of two cultivars of muscadine grapes (Muscadinia rotundifolia (Michx.) Small.) were obtained by hydro-distillation of flowers and berry skins. Twenty-three volatile compounds were identified in essential oils from the muscadine flowers, and twenty volatiles in their corresponding hydrosols. The composition of volatiles in berry skins differed significantly from that of the vine flowers. The antioxidant potential of investigated essential oils and hydrosols was evaluated using five in vitro assays: DPPH (2,2-diphenyl-1-picrylhydrazyl) method, TEAC (Trolox equivalent antioxidant capacity), FRAP (Ferric reducing antioxidant power), CUPRAC (cupric ion reducing antioxidant capacity), and NO (nitric oxide radical scavenging assay). The essential oils from the flowers of both cultivars showed the strongest antioxidant power, whereas the hydrosols were the significantly less active. All investigated essential oils showed very weak antibacterial activities against Bacillus cereus, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. However, the essential oils from the flowers of both cultivars showed moderate antifungal activities against Candida albicans, which were stronger for the oil from “Carlos” (white muscadine cultivar). To the best of our knowledge, this is the first report on obtaining and characterizing essential oils and hydrosols from muscadine grapes. This study demonstrated the variations in aromatic compounds accumulated in flowers and mature berry skins of muscadine grapes, and evaluated their possible antioxidant and antimicrobial activities. The presented results will be the base for future research, focused on a better understanding of the molecular and regulatory mechanisms involved in aromatic compound biosynthesis and accumulation in muscadine grapes. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle
Supercritical Carbon Dioxide (scCO2) Extraction of Phenolic Compounds from Lavender (Lavandula angustifolia) Flowers: A Box-Behnken Experimental Optimization
Molecules 2019, 24(18), 3354; https://doi.org/10.3390/molecules24183354 - 15 Sep 2019
Viewed by 206
Abstract
Due to their numerous health benefits associated with various diseases and anti-oxidation properties, the phenolic compounds collectively referred to as phytochemicals have attracted a lot of interest, however, a single extraction method for polyphenols has not been developed yet. Supercritical fluid extraction, a [...] Read more.
Due to their numerous health benefits associated with various diseases and anti-oxidation properties, the phenolic compounds collectively referred to as phytochemicals have attracted a lot of interest, however, a single extraction method for polyphenols has not been developed yet. Supercritical fluid extraction, a green extraction method, provides the final product without organic solvent residues. In this work the extraction of lavender was performed using supercritical carbon dioxide. A statistical experimental design based on the Box-Behnken (B-B) method was planned, and the extraction yields and total phenolic contents were measured for three different variables: pressure, temperature and extraction time. The ranges were 200–300 bar, 40–60 °C and 15–45 min. The extracts yields from scCO2 extraction were in the range of 4.3–9.2 wt.%. The highest yield (9.2 wt.%) was achieved at a temperature of 60 °C under the pressure of 250 bar after 45 min. It also corresponded to the highest total phenolic content (10.17 mg GAE/g extract). Based on the study, the statistically generated optimal extraction conditions to obtain the highest total phenolic compounds concentration from flowers of Lavandula angustifolia were a temperature of 54.5 °C, pressure of 297.9 bar, and the time of 45 min. Based on the scavenging activity percentage (AA%) of scCO2 extracts, it is concluded that the increase of extraction pressure had a positive influence on the increase of AA% values. Full article
(This article belongs to the Special Issue Recent Advances in Food and Natural Product Analysis)
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Open AccessArticle
In Vitro Evaluation of Antioxidant, Anti-Inflammatory, Antimicrobial and Wound Healing Potential of Thymus Sipyleus Boiss. Subsp. Rosulans (Borbas) Jalas
Molecules 2019, 24(18), 3353; https://doi.org/10.3390/molecules24183353 - 14 Sep 2019
Viewed by 215
Abstract
Thymus sipyleus Boiss. subsp. rosulans (Borbas) Jalas (TS) is a commonly used plant in the treatment of various complaints, including skin wounds in Turkish folk medicine. Despite the widespread traditional use of TS, there is not any scientific report confirming the effectiveness of [...] Read more.
Thymus sipyleus Boiss. subsp. rosulans (Borbas) Jalas (TS) is a commonly used plant in the treatment of various complaints, including skin wounds in Turkish folk medicine. Despite the widespread traditional use of TS, there is not any scientific report confirming the effectiveness of this plant on the healing process. This research aimed to investigate the effects of different extracts obtained from TS on biological events during wound healing, on a cellular basis. In this context, proliferative activities of the extracts, as well as the effects on wound closure and hydroxyproline synthesis, were determined. In addition to wound healing properties, the antioxidant, antibacterial and anti-inflammatory activities of the extracts were evaluated. Decoction (D) and infusion (I) extracts contained the highest amount of phenolic content and showed the most potent activity against DPPH radical. All extracts exhibited complete protection against the damage induced by hydrogen peroxide (H2O2) by increasing cell viability compared to only H2O2-treated groups, both in co-treatment and pre-treatment protocols. None of the extracts exhibited cytotoxic activity, and most of the extracts from the TS stimulated fibroblast proliferation and migration. All TS extracts exert anti-inflammatory activity by suppressing the overproduction of tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO). The most pronounced activity on hydroxyproline synthesis was observed in D extract. In summary, it was observed that TS extracts can promote the healing process by enhancing fibroblast migration, proliferation and collagen synthesis as well as suppressing pro-inflammatory cytokines. The obtained data in this work support the traditional use of TS as a valuable plant-based compound for the treatment of wounds. Full article
(This article belongs to the Special Issue Selected Papers from the Joint Symposia of MESMAP-5 & ISPBS-5)
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Open AccessArticle
Development of a Fragment-Based Screening Assay for the Focal Adhesion Targeting Domain Using SPR and NMR
Molecules 2019, 24(18), 3352; https://doi.org/10.3390/molecules24183352 - 14 Sep 2019
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Abstract
The Focal Adhesion Targeting (FAT) domain of Focal Adhesion Kinase (FAK) is a promising drug target since FAK is overexpressed in many malignancies and promotes cancer cell metastasis. The FAT domain serves as a scaffolding protein, and its interaction with the protein paxillin [...] Read more.
The Focal Adhesion Targeting (FAT) domain of Focal Adhesion Kinase (FAK) is a promising drug target since FAK is overexpressed in many malignancies and promotes cancer cell metastasis. The FAT domain serves as a scaffolding protein, and its interaction with the protein paxillin localizes FAK to focal adhesions. Various studies have highlighted the importance of FAT-paxillin binding in tumor growth, cell invasion, and metastasis. Targeting this interaction through high-throughput screening (HTS) provides a challenge due to the large and complex binding interface. In this report, we describe a novel approach to targeting FAT through fragment-based drug discovery (FBDD). We developed two fragment-based screening assays—a primary SPR assay and a secondary heteronuclear single quantum coherence nuclear magnetic resonance (HSQC-NMR) assay. For SPR, we designed an AviTag construct, optimized SPR buffer conditions, and created mutant controls. For NMR, resonance backbone assignments of the human FAT domain were obtained for the HSQC assay. A 189-compound fragment library from Enamine was screened through our primary SPR assay to demonstrate the feasibility of a FAT-FBDD pipeline, with 19 initial hit compounds. A final total of 11 validated hits were identified after secondary screening on NMR. This screening pipeline is the first FBDD screen of the FAT domain reported and represents a valid method for further drug discovery efforts on this difficult target. Full article
(This article belongs to the Special Issue Fragment Based Drug Discovery)
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Open AccessArticle
Polyamines Disrupt the KaiABC Oscillator by Inducing Protein Denaturation
Molecules 2019, 24(18), 3351; https://doi.org/10.3390/molecules24183351 - 14 Sep 2019
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Abstract
Polyamines are positively charged small molecules ubiquitously existing in all living organisms, and they are considered as one kind of the most ancient cellular components. The most common polyamines are spermidine, spermine, and their precursor putrescine generated from ornithine. Polyamines play critical roles [...] Read more.
Polyamines are positively charged small molecules ubiquitously existing in all living organisms, and they are considered as one kind of the most ancient cellular components. The most common polyamines are spermidine, spermine, and their precursor putrescine generated from ornithine. Polyamines play critical roles in cells by stabilizing chromatin structure, regulating DNA replication, modulating gene expression, etc., and they also affect the structure and function of proteins. A few studies have investigated the impact of polyamines on protein structure and function previously, but no reports have focused on a protein-based biological module with a dedicated function. In this report, we investigated the impact of polyamines (putrescine, spermidine, and spermine) on the cyanobacterial KaiABC circadian oscillator. Using an established in vitro reconstitution system, we noticed that polyamines could disrupt the robustness of the KaiABC oscillator by inducing the denaturation of the Kai proteins (KaiA, KaiB, and KaiC). Further experiments showed that the denaturation was likely due to the induced change of the thermal stability of the clock proteins. Our study revealed an intriguing role of polyamines as a component in complex cellular environments and would be of great importance for elucidating the biological function of polyamines in future. Full article
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Open AccessArticle
Impact of Temperature, Ethanol and Cell Wall Material Composition on Cell Wall-Anthocyanin Interactions
Molecules 2019, 24(18), 3350; https://doi.org/10.3390/molecules24183350 - 14 Sep 2019
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Abstract
The effects of temperature and ethanol concentration on the kinetics of anthocyanin adsorption and desorption interactions with five cell wall materials (CWM) of different composition were investigated. Using temperatures of 15 °C and 30 °C and model wine with ethanol concentrations of 0% [...] Read more.
The effects of temperature and ethanol concentration on the kinetics of anthocyanin adsorption and desorption interactions with five cell wall materials (CWM) of different composition were investigated. Using temperatures of 15 °C and 30 °C and model wine with ethanol concentrations of 0% and 15% (v/v) over 120 min, the adsorption and desorption rates of five anthocyanin-glucosides were recorded in triplicate. Small-scale experiments were conducted using a benchtop incubator to mimic a single berry fermentation. Results indicate that more than 90% of the adsorption occurs within the first 60 min of the addition of anthocyanins to CWM. However, desorption appears to occur much faster, with maximum desorption being reached after 30 min. The extent of both adsorption and desorption was clearly dependent not only on temperature and ethanol concentration but also on the CWM composition. Full article
(This article belongs to the Section Natural Products Chemistry)
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Synthesis of 1,2,3-Triazolium Ionic Liquid-Supported Chiral Imidazolidinones and Their Application in Asymmetric Alkylation Reaction
Molecules 2019, 24(18), 3349; https://doi.org/10.3390/molecules24183349 - 14 Sep 2019
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Abstract
New 1,2,3-triazolium ionic liquid-supported chiral imidazolidinones were developed. The feasibility of the ionic liquid-supported imidazolidinones as chiral auxiliaries was demonstrated in sequential propionylation-alkylation-cleavage reactions, which provided the chiral product with good to excellent chemical yields (up to 90%) and high selectivities (up to [...] Read more.
New 1,2,3-triazolium ionic liquid-supported chiral imidazolidinones were developed. The feasibility of the ionic liquid-supported imidazolidinones as chiral auxiliaries was demonstrated in sequential propionylation-alkylation-cleavage reactions, which provided the chiral product with good to excellent chemical yields (up to 90%) and high selectivities (up to 94% ee). The progress of the reactions could be monitored by TLC and NMR, and the ionic liquid-supported chiral auxiliaries could be recovered by simple extraction. Full article
(This article belongs to the Section Organic Chemistry)
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Surfactant-Switched Positive/Negative Electrorheological Effect in Tungsten Oxide Suspensions
Molecules 2019, 24(18), 3348; https://doi.org/10.3390/molecules24183348 - 14 Sep 2019
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Abstract
The electrorheological (ER) effect was experimentally observed in dielectric suspensions containing tungsten oxide (WO3) modified with surfactant molecules (sodium dodecyl sulfate (SDS) and dodecylamine (DDA)) in electric fields up to several kilovolts per millimeter. The dielectric properties of WO3 suspensions [...] Read more.
The electrorheological (ER) effect was experimentally observed in dielectric suspensions containing tungsten oxide (WO3) modified with surfactant molecules (sodium dodecyl sulfate (SDS) and dodecylamine (DDA)) in electric fields up to several kilovolts per millimeter. The dielectric properties of WO3 suspensions in silicone oil were analyzed, depending on the frequency of the electric field, in the range from 25 to 106 Hz. Unmodified WO3 suspensions, as well as suspensions modified with sodium dodecyl sulfate, were shown to exhibit a positive electrorheological effect, whereas suspensions modified with dodecylamine demonstrated a negative electrorheological effect. The quantitative characteristics of the negative electrorheological effect in the strain–compression and shear regimes were obtained for the first time. Visualization experiments were performed to see the chain structures formed by WO3 particles modified with sodium dodecyl sulfate, as well as for dynamic electroconvection in electrorheological fluids containing WO3 modified with dodecylamine. The negative electrorheological effect was shown to be associated with the processes of phase separation in the electric field, which led to a multiplicative effect and a strong electroconvection of the suspension at field strengths above 1 kV/mm. Full article
(This article belongs to the Section Nanochemistry)
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Open AccessArticle
Mechanochemical Synthesis and Isomerization of N-Substituted Indole-3-carboxaldehyde Oximes
Molecules 2019, 24(18), 3347; https://doi.org/10.3390/molecules24183347 - 14 Sep 2019
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Abstract
Performing solution-phase oximation reactions with hydroxylamine hydrochloride (NH2OH·HCl) carries significant risk, especially in aqueous solutions. In the present study, four N-substituted indole-3-carboxaldehyde oximes were prepared from the corresponding aldehydes by solvent-free reaction with NH2OH·HCl and a base (NaOH [...] Read more.
Performing solution-phase oximation reactions with hydroxylamine hydrochloride (NH2OH·HCl) carries significant risk, especially in aqueous solutions. In the present study, four N-substituted indole-3-carboxaldehyde oximes were prepared from the corresponding aldehydes by solvent-free reaction with NH2OH·HCl and a base (NaOH or Na2CO3) using a mechanochemical approach, thus minimizing the possible risk. In all cases, the conversion to oximes was almost complete. The focus of this work is on 1-methoxyindole-3-carboxaldehyde oxime, a key intermediate in the production of indole phytoalexins with useful antimicrobial properties. Under optimized conditions, it was possible to reach almost 95% yield after 20 min of milling. Moreover, for the products containing electron-donating substituents (-CH3, -OCH3), the isomerization from the oxime anti to syn isomer under acidic conditions was discovered. For the 1-methoxy analog, the acidic isomerization of pure isomers in solution resulted in the formation of anti isomer, whereas the prevalence of syn isomer was observed in solid state. From NMR data the syn and anti structures of produced oximes were elucidated. This work shows an interesting and possibly scalable alternative to classical synthesis and underlines environmentally friendly and sustainable character of mechanochemistry. Full article
(This article belongs to the Special Issue Recent Development of Mechanochemical Synthesis)
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PSTP-3,5-Me Inhibits Osteoclast Differentiation and Bone Resorption
Molecules 2019, 24(18), 3346; https://doi.org/10.3390/molecules24183346 - 14 Sep 2019
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Abstract
Osteogenesis is an orchestrated process regulated by osteoclastogenesis and osteoblastogenesis. Excessive osteoclastogenesis causes bone diseases, such as osteoporosis. Although a few drugs are effective in osteoporosis treatment, these drugs lead to side effects, including cellulitis, flatulence, and hypocalcemia. In this study, we reported [...] Read more.
Osteogenesis is an orchestrated process regulated by osteoclastogenesis and osteoblastogenesis. Excessive osteoclastogenesis causes bone diseases, such as osteoporosis. Although a few drugs are effective in osteoporosis treatment, these drugs lead to side effects, including cellulitis, flatulence, and hypocalcemia. In this study, we reported a 2-(N-Phenylmethylsulfonamido)-N-(2-(phenylthio)phenyl)propanamide (PSTP) compound, PSTP-3,5-Me, as a potential therapeutic agent for osteoporosis. Mouse bone marrow-derived macrophages (BMMs) were differentiated into osteoclasts by receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in the presence of PSTP-3,5-Me. PSTP-3,5-Me inhibited osteoclast differentiation by reduced tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and suppressed the expression of osteoclast marker genes, such as cathepsin K (Ctsk) and TRAP (Acp5). We investigated signaling pathways mediated by RANKL and its receptor, RANK, and found that PSTP-3,5-Me inhibits nucleus translocation of nuclear factor of activated T cell cytoplasmic-1 (NFATc1). Moreover, PSTP-3,5-Me inhibited F-actin ring formation and mineral resorption. Overall, our data suggests that PSTP-3,5-Me attenuates osteoclast differentiation by blocking the activation of NFATc1. Full article
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Open AccessArticle
Profiling of Amino Acids in Urine Samples of Patients Suffering from Inflammatory Bowel Disease by Capillary Electrophoresis-Mass Spectrometry
Molecules 2019, 24(18), 3345; https://doi.org/10.3390/molecules24183345 - 14 Sep 2019
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Abstract
Urine represents a convenient biofluid for metabolomic studies due to its noninvasive collection and richness in metabolites. Here, amino acids are valuable biomarkers for their ability to reflect imbalances of different biochemical pathways. An impact of amino acids on pathology, prognosis and therapy [...] Read more.
Urine represents a convenient biofluid for metabolomic studies due to its noninvasive collection and richness in metabolites. Here, amino acids are valuable biomarkers for their ability to reflect imbalances of different biochemical pathways. An impact of amino acids on pathology, prognosis and therapy of various diseases, including inflammatory bowel disease (IBD), is therefore the subject of current clinical research. This work is aimed to develop a capillary electrophoresis-tandem mass spectrometry (CE-MS/MS) method for the quantification of the 20 proteinogenic amino acids in human urine samples obtained from patients suffering from IBD and treated with thiopurines. The optimized CE-MS/MS method, with minimum sample preparation (just “dilute and shoot”), exhibited excellent linearity for all the analytes (coefficients of determination were higher than 0.99), with inter-day and intra-day precision yielding relative standard deviations in the range of 0.91–15.12% and with accuracy yielding relative errors in the range of 85.47–112.46%. Total analysis time, an important parameter for the sample throughput demanded in routine practice, was shorter in ca. 17% when compared to established CE-MS methods. Favorable performance of the proposed CE-MS/MS method was also confirmed by the comparison with corresponding ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) method. Consistent data for the investigated amino acid metabolome were obtained using both methods. For the first time, the amino acid profiling by CE-MS approach was applied on the clinical IBD samples. Here, significant differences observed in the concentration levels of some amino acids between IBD patients undergoing thiopurine treatment and healthy volunteers could result from the simultaneous action of the disease and the corresponding therapy. These findings indicate that amino acids analysis could be a valuable tool for the study of mechanism of the IBD treatment by thiopurines. Full article
(This article belongs to the Section Analytical Chemistry)
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Polyethersulfone Mats Functionalized with Porphyrin for Removal of Para-nitroaniline from Aqueous Solution
Molecules 2019, 24(18), 3344; https://doi.org/10.3390/molecules24183344 - 14 Sep 2019
Viewed by 203
Abstract
The dispersion of para-nitroaniline (p-NA) in water poses a threat to the environment and human health. Therefore, the development of functional adsorbents to remove this harmful compound is crucial to the implementation of wastewater purification strategies, and electrospun mats represent a versatile and [...] Read more.
The dispersion of para-nitroaniline (p-NA) in water poses a threat to the environment and human health. Therefore, the development of functional adsorbents to remove this harmful compound is crucial to the implementation of wastewater purification strategies, and electrospun mats represent a versatile and cost-effective class of materials that are useful for this application. In the present study, we tested the ability of some polyethersulfone (PES) nanofibers containing adsorbed porphyrin molecules to remove p-NA from water. The functional mats in this study were obtained by two different approaches based on fiber impregnation or doping. In particular, meso-tetraphenyl porphyrin (H2TPP) or zinc(II) meso-tetraphenyl porphyrin (ZnTPP) were immobilized on the surface of PES fiber mats by dip-coating or added to the PES electrospun solution to obtain porphyrin-doped PES mats. The presence of porphyrins on the fiber surfaces was confirmed by UV–Vis spectroscopy, fluorescence measurements, and XPS analysis. p-NA removal from water solutions was spectrophotometrically detected and evaluated. Full article
(This article belongs to the Special Issue Spatial Organization of Multi-Porphyrins for Pre-Defined Properties)
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