bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-osteoarthritic Effects of an Herbal Composition LI73014F2 on Interleukin-1β-induced Primary Human Articular Chondrocytes
Authors: Kim Hae Lim , Lee Hae Jin , Lee Dong-Ryung , Choi Bong-Keun , Yang Seung Hwan
Published: April 2020

Osteoarthritis (OA) is one of the most well-characterized joint diseases and is associated with chondrocyte inflammation, metalloproteinase upregulation and apoptosis. LI73014F2 is a novel composition prepared from aqueous extract of Terminalia chebula fruit, alcohol extract of Curcuma longa rhizome, and Boswellia serrata extract at 2:1:2 ratio. Earlier studies have shown that LI73014F2 inhibits cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) activities, and attenuates clinical symptoms in OA subjects. In the present study, we evaluated the protective anti-inflammatory and anti-apoptotic effects, as well as the underlying mechanisms, of LI73014F2 in interleukin (IL)-1β-induced inflammation in human primary chondrocytes. Human chondrocytes were treated with LI73014F2 (0, 12.5, 25 and 50 μg/mL) in IL-1β (10 ng/mL)-containing chondrocyte growth medium for 24 h. Cell viability was assessed using an MTT assay. The pro-inflammatory mediator, inflammatory cytokines, MMPs, apoptosis-related proteins, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways protein expression levels were detected by western blot analysis. The results demonstrated that LI73014F2 normalized the expressions of COX-2, mPGES-1, PGE2, 5-LOX, LTB4, IL-1β, TNFα, IL-6, MMP-2, MMP-3, MMP-9, MMP-13, Bax/Bcl-2, cleaved caspase-9 and -3, cleaved PARP, phospho-NF-κB p65 and phospho-p38 MAPK proteins in IL-1β-induced primary human chondrocytes. Moreover, the data suggested that LI73014F2 reduced IL-1β-induced inflammation and apoptosis, at least partially via the inhibition of the NF-κB/MAPK signaling pathway. In conclusion, the present findings provide the molecular basis of the anti-OA efficacy of LI73014F2.
Development of UHPLC-MS/MS Method for Indirubin-3′-Oxime Derivative as a Novel FLT3 Inhibitor and Pharmacokinetic Study in Rats
Authors: Kim Na Yoon , Kim Yong-Chul , Kim Yoon Gyoon
Published: April 2020

This study aimed to develop and validate a sensitive liquid chromatography-coupled tandem mass spectrometry method for the quantification of LDD-2614, an indirubin derivative and novel FLT3 inhibitor, in rat plasma. In addition, the developed analytical method was applied to observe the pharmacokinetic properties of LDD-2614. Chromatographic separation was achieved on a Luna omega C18 column using a mixture of water and acetonitrile, both containing 0.1% formic acid. Quantitation was performed using positive electrospray ionization in a multiple reaction monitoring (MRM) mode. The MRM transitions were optimized as m/z 426.2→113.1 for LDD-2614 and m/z 390.2→113.1 for LDD-2633 (internal standard), and the lower limit of quantification (LLOQ) for LDD-2614 was determined as 0.1 ng/mL. Including the LLOQ, the nine-point calibration curve was linear with a correlation coefficient greater than 0.9991. Inter- and intraday accuracies (RE) ranged from −3.19% to 8.72%, and the precision was within 9.02%. All validation results (accuracy, precision, matrix effect, recovery, stability, and dilution integrity) met the acceptance criteria of the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety guidelines. The proposed method was validated and demonstrated to be suitable for the quantification of LDD-2614 for pharmacokinetics studies.
Isofraxidin: Synthesis, Biosynthesis, Isolation, Pharmacokinetic and Pharmacological Properties
Authors: Majnooni Mohammad Bagher , Fakhri Sajad , Shokoohinia Yalda , Mojarrab Mahdi , Kazemi-Afrakoti Sara , Farzaei Mohammad Hosein
Published: April 2020

Isofraxidin (7-hydroxy-6, 8-dimethoxy coumarin) (IF) is a hydroxy coumarin with several biological and pharmacological activities. The plant kingdom is of the most prominent sources of IF, which, among them, Eleutherococcus and Fraxinus are the well-known genera in which IF could be isolated/extracted from their species. Considering the complex pathophysiological mechanisms behind some diseases (e.g., cancer, neurodegenerative diseases, and heart diseases), introducing IF as a potent multi-target agent, which possesses several herbal sources and the multiple methods for isolation/purification/synthesis, along with the unique pharmacokinetic profile and low levels of side effects, could be of great importance. Accordingly, a comprehensive review was done without time limitations until February 2020. IF extraction methods include microwave, mechanochemical, and ultrasound, along with other conventional methods in the presence of semi-polar solvents such as ethyl acetate (EtOAc). In addition to the isolation methods, related synthesis protocols of IF is also of great importance. From the synthesis point of view, benzaldehyde derivatives are widely used as precursors for IF synthesis. Along with the methods of isolation and biosynthesis, IF pharmacokinetic studies showed hopeful in vivo results of its rapid absorption after oral uses, leading to different pharmacological effects. In this regard, IF targets varieties of inflammatory mediators including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-α (TNF-α), and matrix metalloproteinases (MMPs). thereby indicating anticancer, cardioprotective, and neuroprotective effects. This is the first review on the synthesis, biosynthesis, isolation, and pharmacokinetic and pharmacological properties of IF in combating different diseases.
Genistin: A Novel Potent Anti-Adipogenic and Anti-Lipogenic Agent
Authors: Choi Yae , Shim Jaewon , Kim Min
Published: April 2020

Soy isoflavones are popular ingredients with anti-adipogenic and anti-lipogenic properties. The anti-adipogenic and anti-lipogenic properties of genistein are well-known, but those of genistin and glycitein remain unknown, and those of daidzein are characterized by contrasting data. Therefore, the purpose of our study was to investigate the effects of daidzein, glycitein, genistein, and genistin on adipogenesis and lipogenesis in 3T3-L1 cells. Proliferation of 3T3-L1 preadipocytes was unaffected by genistin and glycitein, but it was affected by 50 and 100 µM genistein and 100 µM daidzein for 48 h. Among the four isoflavones, only 50 and 100 µM genistin and genistein markedly suppressed lipid accumulation during adipogenesis in 3T3-L1 cells through a similar signaling pathway in a dose-dependent manner. Genistin and genistein suppress adipocyte-specific proteins and genes, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), and adipocyte binding protein 2 (aP2)/fatty acid-binding protein 4 (FABP4), and lipogenic enzymes such as ATP citrate lyase (ACL), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FAS). Both isoflavones also activate AMP-activated protein kinase α (AMPKα), an essential factor in adipocyte differentiation, and inhibited sterol regulatory element-binding transcription factor 1c (SREBP-1c). These results indicate that genistin is a potent anti-adipogenic and anti-lipogenic agent.
Fluorescence Detection of Deoxyadenosine in Cordyceps spp. by Indicator Displacement Assay
Authors: Dewantari Arinta Agnie , Yongwattana Nattha , Payongsri Panwajee , Seemakhan Sawinee , Borwornpinyo Suparerk , Ojida Akio , Wongkongkatep Jirarut
Published: April 2020

A rapid, sensitive and reliable indicator displacement assay (IDA) for specific detection of 2′- and 3′-deoxyadenosine (2′-dAde and 3′-dAde), the latter is also known as cordycepin, was established. The formation of inclusion complex between protonated acridine orange (AOH+) and cucurbit[7]uril (CB7) resulted in the hypochromic shift of fluorescent emission from 530 nm to 512 nm. Addition of cordycepin to the highly fluorescent AOH+/CB7 complex resulted in a unique tripartite AOH+/CB7/dAde complex with diminished fluorescence, and such reduction in emission intensity serves as the basis for our novel sensing system. The detection limits were 11 and 82 μM for 2′- and 3′-deoxyadenosine, respectively. The proposed method also demonstrated high selectivity toward 2′- and 3′-deoxyadenosine, owing to the inability of other deoxynucleosides, nucleosides and nucleotides commonly found in Cordyceps spp. to displace the AOH+ from the AOH+/CB7 complex, which was confirmed by isothermal titration calorimetry (ITC), UV-Visible and proton nuclear magnetic resonance (1H-NMR) spectroscopy. Our method was successfully implemented in the analysis of cordycepin in commercially available Ophiocordyceps and Cordyceps supplements, providing a novel and effective tool for quality assessment of these precious fungi with several health benefits.
Recent Advances in Studying Interfacial Adsorption of Bioengineered Monoclonal Antibodies
Authors: Hollowell Peter , Li Zongyi , Hu Xuzhi , Ruane Sean , Kalonia Cavan , van der Walle Christopher F. , Lu Jian R.
Published: April 2020

Monoclonal antibodies (mAbs) are an important class of biotherapeutics; as of 2020, dozens are commercialized medicines, over a hundred are in clinical trials, and many more are in preclinical developmental stages. Therapeutic mAbs are sequence modified from the wild type IgG isoforms to varying extents and can have different intrinsic structural stability. For chronic treatments in particular, high concentration (≥ 100 mg/mL) aqueous formulations are often preferred for at-home administration with a syringe-based device. MAbs, like any globular protein, are amphiphilic and readily adsorb to interfaces, potentially causing structural deformation and even unfolding. Desorption of structurally perturbed mAbs is often hypothesized to promote aggregation, potentially leading to the formation of subvisible particles and visible precipitates. Since mAbs are exposed to numerous interfaces during biomanufacturing, storage and administration, many studies have examined mAb adsorption to different interfaces under various mitigation strategies. This review examines recent published literature focusing on adsorption of bioengineered mAbs under well-defined solution and surface conditions. The focus of this review is on understanding adsorption features driven by distinct antibody domains and on recent advances in establishing model interfaces suitable for high resolution surface measurements. Our summary highlights the need to further understand the relationship between mAb interfacial adsorption and desorption, solution aggregation, and product instability during fill-finish, transport, storage and administration.
Two Annulated Azaheterocyclic Cores Readily Available from a Single Tetrahydroisoquinolonic Castagnoli–Cushman Precursor
Authors: Karchuganova Elizaveta , Bakulina Olga , Dar’in Dmitry , Krasavin Mikhail
Published: April 2020

A novel approach to indolo[3,2-c]isoquinoline and dibenzo[c,h][1,6]naphthyridine tetracyclic systems was discovered based on switchable reduction of 2-methoxy-3-(2-nitrophenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid prepared via Castagnoli–Cushman reaction. Reduction with ammonium formate resulted in the expected selective transformation of the nitro group (thus providing access to substituted dibenzo[c,h][1,6]naphthyridine via cyclization and dehydrogenation). However, attempted reduction with sodium sulfide initiated a previously unknown reaction cascade including double reduction, cyclization, and decarboxylation, leading to formation of indolo[3,2-c]isoquinoline polyheterocycle in one synthetic step.
Synthesis, Electrochemical and Spectroscopic Characterization of Selected Quinolinecarbaldehydes and Their Schiff Base Derivatives
Authors: Wantulok Jakub , Szala Marcin , Quinto Andrea , Nycz Jacek E. , Giannarelli Stefania , Sokolová Romana , Książek Maria , Kusz Joachim
Published: April 2020

A new approach to the synthesis of selected quinolinecarbaldehydes with carbonyl groups located at C5 and/or in C7 positions is presented in this paper in conjunction with spectroscopic characterization of the products. The classical Reimer-Tiemann, Vilsmeier-Haack and Duff aldehyde synthesis methods were compared due to their importance. Computational studies were carried out to explain the preferred selectivity of the presented formylation transformations. A carbene insertion reaction based on Reimer-Tiemann methodology is presented for making 7-bromo-8-hydroxyquinoline-5-carbaldehyde. Additionally, Duff and Vilsmeier-Haack reactions were used in the double formylation of quinoline derivatives and their analogues benzo[h]quinolin-10-ol, 8-hydroxy-2-methylquinoline-5,7-dicarbaldehyde, 8-(dimethylamino) quinoline-5,7-dicarbaldehyde and 10-hydroxybenzo[h]quinoline-7,9-dicarbaldehyde. Four Schiff base derivatives of 2,6-diisopropylbenzenamine were prepared from selected quinoline-5-carbaldehydes and quinoline-7-carbaldehyde by an efficient synthesis protocol. Their properties have been characterized by a combination of several techniques: MS, HRMS, GC-MS, FTIR, electronic absorption spectroscopy and multinuclear NMR. The electrochemical properties of 8-hydroxy-quinoline-5-carbaldehyde, 6-(dimethylamino)quinoline-5-carbaldehyde and its methylated derivative were investigated, and a strong correlation between the chemical structure and obtained reduction and oxidation potentials was found. The presence of a methyl group facilitates oxidation. In contrast, the reduction potential of methylated compounds was more negative comparing to non-methylated structure. Calculations of frontier molecular orbitals supported the finding. The structures of 8-hydroxy-2-methylquinoline-5,7-dicarbaldehyde and four Schiff bases were determined by single-crystal X-ray diffraction measurements.
Dalbergia ecastaphyllum (L.) Taub. and Symphonia globulifera L.f.: The Botanical Sources of Isoflavonoids and Benzophenones in Brazilian Red Propolis
Authors: Ccana-Ccapatinta Gari Vidal , Mejía Jennyfer Andrea Aldana , Tanimoto Matheus Hikaru , Groppo Milton , Carvalho Jean Carlos Andrade Sarmento de , Bastos Jairo Kenupp
Published: April 2020

The Brazilian red propolis (BRP) constitutes an important commercial asset for northeast Brazilian beekeepers. The role of Dalbergia ecastaphyllum (L.) Taub. (Fabaceae) as the main botanical source of this propolis has been previously confirmed. However, in addition to isoflavonoids and other phenolics, which are present in the resin of D. ecastaphyllum, samples of BRP are reported to contain substantial amounts of polyprenylated benzophenones, whose botanical source was unknown. Therefore, field surveys, phytochemical and chromatographic analyses were undertaken to confirm the botanical sources of the red propolis produced in apiaries located in Canavieiras, Bahia, Brazil. The results confirmed D. ecastaphyllum as the botanical source of liquiritigenin (1), isoliquiritigenin (2), formononetin (3), vestitol (4), neovestitol (5), medicarpin (6), and 7-O-neovestitol (7), while Symphonia globulifera L.f. (Clusiaceae) is herein reported for the first time as the botanical source of polyprenylated benzophenones, mainly guttiferone E (8) and oblongifolin B (9), as well as the triterpenoids β-amyrin (10) and glutinol (11). The chemotaxonomic and economic significance of the occurrence of polyprenylated benzophenones in red propolis is discussed.
Pharmacological (or Synthetic) and Nutritional Agonists of PPAR-γ as Candidates for Cytokine Storm Modulation in COVID-19 Disease
Authors: Ciavarella Carmen , Motta Ilenia , Valente Sabrina , Pasquinelli Gianandrea
Published: April 2020

The cytokine storm is an abnormal production of inflammatory cytokines, due to the over-activation of the innate immune response. This mechanism has been recognized as a critical mediator of influenza-induced lung disease, and it could be pivotal for COVID-19 infections. Thus, an immunomodulatory approach targeting the over-production of cytokines could be proposed for viral aggressive pulmonary disease treatment. In this regard, the peroxisome proliferator-activated receptor (PPAR)-γ, a member of the PPAR transcription factor family, could represent a potential target. Beside the well-known regulatory role on lipid and glucose metabolism, PPAR-γ also represses the inflammatory process. Similarly, the PPAR-γ agonist thiazolidinediones (TZDs), like pioglitazone, are anti-inflammatory drugs with ameliorating effects on severe viral pneumonia. In addition to the pharmacological agonists, also nutritional ligands of PPAR-γ, like curcuma, lemongrass, and pomegranate, possess anti-inflammatory properties through PPAR-γ activation. Here, we review the main synthetic and nutritional PPAR-γ ligands, proposing a dual approach based on the strengthening of the immune system using pharmacological and dietary strategies as an attempt to prevent/treat cytokine storm in the case of coronavirus infection.
New 8-C-p-Hydroxylbenzylflavonol Glycosides from Pumpkin (Cucurbita moschata Duch.) Tendril and Their Osteoclast Differentiation Inhibitory Activities
Authors: Kim Kiok , Choi Joo-Hee , Oh Jisu , Park Ji-Yeon , Kim Young-Min , Moon Jae-Hak , Park Jong-Hwan , Cho Jeong-Yong
Published: April 2020

Six new 8-C-p-hydroxybenzylflavonol glycosides were isolated from a hot water extract of pumpkin (Cucurbita moschata Duch.) tendril and elucidated as 8-C-p-hydroxybenzylquercetin 3-O-rutinoside, 8-C-p-hydroxybenzoylquercetin 3-O-β-D-glucopyranoside, 8-C-p-hydroxybenzylkaempferol 3-O-(α-L-rhamnopyranosyl(1→6)-β-D-galactopyranoside, 8-C-p-hydroxybenzoylkaempferol 3-O-rutinoside, 8-C-p-hydroxybenzylisorhamnetin 3-O-rutinoside, and 8-C-p-hydroxybenzylisorhamnetin 3-O-(α-L-rhamnopyranosyl(1→6)-β-D-galactopyranoside. Their chemical structures were determined using nuclear magnetic resonance (NMR) and electrospray ionization-mass spectrometer (ESIMS) analyses. The 8-C-p-hydroxybenzylflavonol glycosides were found to inhibit the receptor activator of nuclear factor-κB (RANKL)-induced osteoclast differentiation of bone marrow derived macrophage (BMDM), an osteoclast progenitor. Additionally, 8-C-p-hydroxybenzylflavonol glycosides effectively reduced the expression of osteoclast-related genes, such as tartrate-resistant acid phosphatase, cathepsin K, nuclear factor activated T-cell cytoplasmic 1, and dendritic cell specific transmembrane protein in RANKL-treated BMDMs. These results indicate that the 8-C-p-hydroxybenzylflavonol glycosides may be the main components responsible for the osteoclast differentiation inhibitory effect of pumpkin tendril.
Mangiferin Rich Products from Aphloia theiformis (Vahl) Benn Leaves: Extraction, Fractionation, Phytochemical Characterization, and Antioxidant Properties
Authors: Grauzdytė Dovilė , Pukalskas Audrius , El Kalamouni Chaker , Venskutonis Petras Rimantas
Published: April 2020

Aphloia theiformis is traditionally used in Mauritius, Madagascar, and Reunion Island for treating several diseases. In this study, various extraction solvents and schemes were applied for the recovery of antioxidant rich fractions from the leaves of A. theiformis. The products were evaluated for their antioxidant capacity using well known in vitro assays. Major compounds were characterized by UPLC–QTOF–MS. Hydrophilic extracts of A. theiformis demonstrated strong antioxidant properties, which are comparable with the synthetic antioxidant Trolox. UPLC analysis confirmed mangiferin as the main secondary metabolite of A. theiformis. Tormentic and hydroxytormentic acids as well as their isomers were also abundant in A. theiformis extracts and fractions, while their amounts were determined for the first time. The most potential extract was further separated into the fractions by liquid-liquid extraction and by precipitation at low temperature. Antioxidant capacity and composition of secondary metabolites of derived fractions were determined. Some of the fractions possessed remarkable antioxidant capacity, comparable to pure mangiferin. The results obtained reveal high potential of A. theiformis for recovery of natural antioxidants and other bioactive phytochemicals, particularly mangiferin.
Tricin Isolated from Enzyme-Treated Zizania latifolia Extract Inhibits IgE-Mediated Allergic Reactions in RBL-2H3 Cells by Targeting the Lyn/Syk Pathway
Authors: Lee Jae-Yeul , Park Se-Ho , Jhee Kwang-Hwan , Yang Seun-Ah
Published: April 2020

Tricin, a flavone present in rice bran, is confirmed as the major efficacious compound present in the enzyme-treated Zizania latifolia extract (ETZL), which protects against UVB-induced skin-aging. However, the suppressive mechanism of tricin on allergic responses remains unknown. The present study, therefore, aimed to determine the mechanisms of tricin and ETZL on mast cell degranulation in IgE-activated rat basophilic leukemia cell line (RBL-2H3) cells. We investigated the regulatory effects of tricin and ETZL on degranulation, production of cytokines and lipid mediators, and signaling proteins involved in the IgE-bound high-affinity IgE receptor activation, mitogen-activated protein kinase, arachidonic acid and Syk. The production of β–hexosaminidase, tumor necrosis factor-α, interleukin-4, leukotrienes (LT) B4, LTC4 and prostaglandin E2 in IgE-stimulated RBL-2H3 cells were significantly inhibited by exposure to tricin or ETZL. Moreover, tricin and ETZL inhibit the phosphorylation of cytosolic phospholipase A2, 5-lipoxygenase and cyclooxygenase-2. Furthermore, the phosphorylation of Akt, ERK, p38, JNK, protein kinase Cδ and phospholipase Cγ1 were effectively suppressed by both samples. Exposure to tricin or ETZL also significantly decreases the phosphorylation of Lyn and Syk, but has minimal effect on Fyn. Taken together, our data indicate that tricin and ETZL are potential anti-allergic materials that could be applied for the prevention of allergy-related diseases.
Mechanistic Understanding of Peptide Analogues, DALDA, [Dmt1]DALDA, and KGOP01, Binding to the Mu Opioid Receptor
Authors: Dumitrascuta Maria , Bermudez Marcel , Ballet Steven , Wolber Gerhard , Spetea Mariana
Published: April 2020

The mu opioid receptor (MOR) is the primary target for analgesia of endogenous opioid peptides, alkaloids, synthetic small molecules with diverse scaffolds, and peptidomimetics. Peptide-based opioids are viewed as potential analgesics with reduced side effects and have received constant scientific interest over the years. This study focuses on three potent peptide and peptidomimetic MOR agonists, DALDA, [Dmt1]DALDA, and KGOP01, and the prototypical peptide MOR agonist DAMGO. We present the first molecular modeling study and structure–activity relationships aided by in vitro assays and molecular docking of the opioid peptide analogues, in order to gain insight into their mode of binding to the MOR. In vitro binding and functional assays revealed the same rank order with KGOP01 > [Dmt1]DALDA > DAMGO > DALDA for both binding and MOR activation. Using molecular docking at the MOR and three-dimensional interaction pattern analysis, we have rationalized the experimental outcomes and highlighted key amino acid residues responsible for agonist binding to the MOR. The Dmt (2′,6′-dimethyl-L-Tyr) moiety of [Dmt1]DALDA and KGOP01 was found to represent the driving force for their high potency and agonist activity at the MOR. These findings contribute to a deeper understanding of MOR function and flexible peptide ligand–MOR interactions, that are of significant relevance for the future design of opioid peptide-based analgesics.
Recent Advances in Luminescence Imaging of Biological Systems Using Lanthanide(III) Luminescent Complexes
Authors: Monteiro Jorge H. S. K.
Published: April 2020

The use of luminescence in biological systems allows one to diagnose diseases and understand cellular processes. Molecular systems, particularly lanthanide(III) complexes, have emerged as an attractive system for application in cellular luminescence imaging due to their long emission lifetimes, high brightness, possibility of controlling the spectroscopic properties at the molecular level, and tailoring of the ligand structure that adds sensing and therapeutic capabilities. This review aims to provide a background in luminescence imaging and lanthanide spectroscopy and discuss selected examples from the recent literature on lanthanide(III) luminescent complexes in cellular luminescence imaging, published in the period 2016–2020. Finally, the challenges and future directions that are pointing for the development of compounds that are capable of executing multiple functions and the use of light in regions where tissues and cells have low absorption will be discussed.
Glass-Forming Ability and Soft Magnetic Properties of (Co75Ti25)100−xFex (x; 0–20 at.%) Systems Fabricated by SPS of Mechanically Alloyed Nanopowders
Authors: El-Eskandarany Mohamed Sherif , Ali Naser , Saeed Maryam
Published: April 2020

Due to their outstanding mechanical properties and soft magnetic characteristics, cobalt-based metallic glassy alloys have stimulated much interesting research. These metastable ferromagnetic materials possess very small magnetocrystalline anisotropy, and almost zero magnetostriction. They reveal low coercivity, extremely low core loss, moderate saturation polarization, and very high magnetism. Despite these attractive physical behaviors, Co-based metallic glasses are difficult to obtain by the melting/casting and conventional rapid solidification techniques due to their poor glass-forming ability. In the present study, we succeed in preparing (Co75Ti25)100−xFex (x; 0–20 at.%) metallic glassy powders, using a mechanical alloying approach. The end product of the as-prepared powders was consolidated into full dense cylinders with large-diameter and thickness (2 × 2 cm), using spark plasma sintering technique. The results have shown that the consolidation step did not lead to any undesired crystallizations or phase transformations, and the as-consolidated buttons maintained their unique short-range order structure. These bulk metallic glassy systems possessed high glass-transition and crystallization temperatures, suggesting their high thermal stability. However, they showed low values of the reduced glass-transition temperatures, indicating that this system is difficult to prepare by the conventional way of preparations.
Polyelectrolyte Multilayer Films Modification with Ag and rGO Influences Platelets Activation and Aggregate Formation under In Vitro Blood Flow
Authors: Imbir Gabriela , Mzyk Aldona , Trembecka-Wójciga Klaudia , Jasek-Gajda Ewa , Plutecka Hanna , Schirhagl Romana , Major Roman
Published: April 2020

Surface functionalization of materials to improve their hemocompatibility is a challenging problem in the field of blood-contacting devices and implants. Polyelectrolyte multilayer films (PEMs), which can mimic functions and structure of an extracellular matrix (ECM), are a promising solution to the urgent need for functional blood-contacting coatings. The properties of PEMs can be easily tuned in order to provide a scaffold with desired physico-chemical parameters. In this study chitosan/chondroitin sulfate (Chi/CS) polyelectrolyte multilayers were deposited on medical polyurethane. Afterwards PEMs were modified by chemical cross-linking and nanoparticles introduction. Coatings with variable properties were tested for their hemocompatibility in the cone-plate tester under dynamic conditions. The obtained results enable the understanding of how substrate properties modulate PEMs interaction with blood plasma proteins and the morphotic elements.
The Terahertz Dynamics of an Aqueous Nanoparticle Suspension: An Inelastic X-ray Scattering Study
Authors: De Francesco Alessio , Scaccia Luisa , Formisano Ferdinando , Guarini Eleonora , Bafile Ubaldo , Maccarini Marco , Alatas Ahmet , Cai Yong Q. , Cunsolo Alessandro
Published: April 2020

We used the high-resolution Inelastic X-ray Scattering beamline of the Advanced Photon Source at Argonne National Laboratory to measure the terahertz spectrum of pure water and a dilute aqueous suspension of 15 nm diameter spherical Au nanoparticles (Au-NPs). We observe that, despite their sparse volume concentration of about 0.5%, the immersed NPs strongly influence the collective molecular dynamics of the hosting liquid. We investigate this effect through a Bayesian inference analysis of the spectral lineshape, which elucidates how terahertz transport properties of water change upon Au-NP immersion. In particular, we observe a nearly complete disappearance of the longitudinal acoustic mode and a mildly decreased ability to support shear wave propagation.
Deciphering the Role of Polyphenols in Sports Performance: From Nutritional Genomics to the Gut Microbiota toward Phytonutritional Epigenomics
Authors: Sorrenti Vincenzo , Fortinguerra Stefano , Caudullo Giada , Buriani Alessandro
Published: April 2020

The individual response to nutrients and non-nutrient molecules can be largely affected by three important biological layers. The gut microbiome can alter the bioavailability of nutrients and other substances, the genome can influence molecule kinetics and dynamics, while the epigenome can modulate or amplify the properties of the genome. Today the use of omic techniques and bioinformatics, allow the construction of individual multilayer networks and thus the identification of personalized strategies that have recently been considered in all medical fields, including sports medicine. The composition of each athlete’s microbiome influences sports performance both directly by acting on energy metabolism and indirectly through the modulation of nutrient or non-nutrient molecule availability that ultimately affects the individual epigenome and the genome. Among non-nutrient molecules polyphenols can potentiate physical performances through different epigenetic mechanisms. Polyphenols interact with the gut microbiota, undergoing extensive metabolism to produce bioactive molecules, which act on transcription factors involved in mitochondrial biogenesis, antioxidant systems, glucose and lipid homeostasis, and DNA repair. This review focuses on polyphenols effects in sports performance considering the individual microbiota, epigenomic asset, and the genomic characteristics of athletes to understand how their supplementation could potentially help to modulate muscle inflammation and improve recovery.
Hydrogel-Based Active Substance Release Systems for Cosmetology and Dermatology Application: A Review
Authors: Zagórska-Dziok Martyna , Sobczak Marcin
Published: April 2020

Hydrogels are playing an increasingly important role in medicine and pharmacy. Due to their favorable physicochemical properties, biocompatibility, and designed interaction with living surroundings, they seem to be one of the most promising groups of biomaterials. Hydrogel formulations from natural, semi, or synthetic polymeric materials have gained great attention in recent years for treating various dermatology maladies and for cosmetology procedures. The purpose of this review is to present a brief review on the basic concept of hydrogels, synthesis methods, relevant mechanisms, and applications in dermatology or cosmetology. This review discusses transdermal therapies and the recent advances that have occurred in the field.
Quercetin Is a Flavonoid Breast Cancer Resistance Protein Inhibitor with an Impact on the Oral Pharmacokinetics of Sulfasalazine in Rats
Authors: Song Yoo-Kyung , Yoon Jin-Ha , Woo Jong Kyu , Kang Ju-Hee , Lee Kyeong-Ryoon , Oh Seung Hyun , Chung Suk-Jae , Maeng Han-Joo
Published: April 2020

The potential inhibitory effect of quercetin, a major plant flavonol, on breast cancer resistance protein (BCRP) activity was investigated in this study. The presence of quercetin significantly increased the cellular accumulation and associated cytotoxicity of the BCRP substrate mitoxantrone in human cervical cancer cells (HeLa cells) in a concentration-dependent manner. The transcellular efflux of prazosin, a stereotypical BCRP substrate, was also significantly reduced in the presence of quercetin in a bidirectional transport assay using human BCRP-overexpressing cells; further kinetic analysis revealed IC50 and Ki values of 4.22 and 3.91 μM, respectively. Moreover, pretreatment with 10 mg/kg quercetin in rats led to a 1.8-fold and 1.5-fold increase in the AUC8h (i.e., 44.5 ± 11.8 min∙μg/mL vs. 25.7 ± 9.98 min∙μg/mL, p < 0.05) and Cmax (i.e., 179 ± 23.0 ng/mL vs. 122 ± 23.2 ng/mL, p < 0.05) of orally administered sulfasalazine, respectively. Collectively, these results provide evidence that quercetin acts as an in vivo as well as in vitro inhibitor of BCRP. Considering the high dietary intake of quercetin as well as its consumption as a dietary supplement, issuing a caution regarding its food–drug interactions should be considered.
Quality by Design for the Development and Analysis of Enhanced In-Situ Forming Vesicles for the Improvement of the Bioavailability of Fexofenadine HCl In Vitro and In Vivo
Authors: Nasr Ali M. , Qushawy Mona K. , Elkhoudary Mahmoud M. , Gawish Aya Y. , Elhady Sameh S. , Swidan Shady A.
Published: April 2020

Drug absorption from the gastrointestinal tract (GIT) is one of the major problems affecting the bioavailability of orally absorbed drugs. This work aims to enhance Fexofenadine HCl oral bioavailability in vivo, the drug used for allergic rhinitis. In this study, novel spray-dried lactose-based enhanced in situ forming vesicles were prepared using different absorption enhancer by the slurry method. Full factorial design was used to obtain an optimized formulation, while central composite design was used to develop economic, environment-friendly analysis method of Fexofenadine HCl in plasma of rabbits. The optimized formulation containing Capryol 90 as absorption enhancer has a mean particle size 202.6 ± 3.9 nm and zeta potential −31.6 ± 0.9 mV. It achieved high entrapment efficiency of the drug 73.7 ± 1.7% and rapid Q3h release reaches 71.5 ± 2.7%. The design-optimized HPLC assay method in rabbit plasma could separate Fexofenadine HCl from endogenous plasma compounds in less than 3.7 min. The pharmacokinetic study and the pharmacological effect of the fexofenadine-loaded optimized formulation showed a significant increase in blood concentration and significantly higher activity against compound 48/80 induced systemic anaphylaxis-like reactions in mice. Therefore, enhanced in situ forming vesicles were effective nanocarriers for the entrapment and delivery of Fexofenadine HCl.
A Smart Strategy to Improve t-Resveratrol Production in Grapevine Cells Treated with Cyclodextrin Polymers Coated with Magnetic Nanoparticles
Authors: Almagro Lorena , Gea-Abellán Alicia De , Rodríguez-López María Isabel , Núñez-Delicado Estrella , Gabaldón José Antonio , Pedreño María Angeles
Published: April 2020

One of the most successfully procedures used to increase the production of t-resveratrol in Vitis vinifera suspension-cultured cells is the application of cyclodextrins (CDs) and methyl jasmonate (MJ) as elicitors. In particular, β-CDs are characterized by their chemical structure which makes them special, not only by acting as elicitors, but also because they are compounds capable of trapping high added-value hydrophobic molecules such as t-resveratrol. However, the use of β-CDs as elicitors increases the production costs of this compound, making their industrial exploitation economically unfeasible. Therefore, the development of β-CDs recovery strategies is necessary to provide a viable solution to their industrial use. In this work, carboxymethylated and hydroxypropylated β-CDs have been used to form polymers using epichlorohydrin (EPI) as a cross-linking agent. The polymers were coated to Fe3O4 nanoparticles and were jointly used with MJ to elicit V. vinifera suspension-cultured cells. Once elicitation experiments were finished, a magnet easily allowed the recovery of polymers, and t-resveratrol was extracted from them by using ethyl acetate. The results indicated that the production of t-resveratrol in the presence of free carboxymethyl-β-CDs was much lower than that found in the presence of carboxymethyl-β-cyclodextrins-EPI polymer coated magnetic nanoparticles. In addition, the maximal levels of t-resveratrol were found at 168 h of elicitation in the presence of 15 g/L hydroxypropyl-β-CDs polymer coated magnetic nanoparticles and MJ, and non-t-resveratrol was found in the extracellular medium, indicating that all the t-resveratrol produced by the cells and secreted into the culture medium was trapped by the polymer and extracted from it. This work also showed that polymers can be regenerated and reused during three cycles of continuous elicitation since the induction and adsorption capacity of hydroxypropyl-β-CDs polymer-coated magnetic nanoparticles after these cycles of elicitation remained high, allowing high concentrations of t-resveratrol to be obtained.
Non-Invasive Approaches for the Evaluation of the Functionalization of Melamine Foams with In-Situ Synthesized Silver Nanoparticles
Authors: Barroso-Solares Suset , Cimavilla-Roman Paula , Rodriguez-Perez Miguel Angel , Pinto Javier
Published: April 2020

The use of polymeric nanocomposites has arisen as a promising solution to take advantage of the properties of nanoparticles (NPs) in diverse applications (e.g., water treatment, catalysis), while overcoming the drawbacks of free-standing nanoparticles (e.g., aggregation or accidental release). In most of the cases, the amount and size of the NPs will affect the stability of the composite as well as their performance. Therefore, a detailed characterization of the NPs present on the nanocomposites, including their quantification, is of vital importance for the optimization of these systems. However, the determination of the NPs load is often carried out by destructive techniques such as TGA or ICP-OES, the development of non-invasive approaches to that aim being necessary. In this work, the amount of silver NPs synthesized directly on the surface of melamine (ME) foams is studied using two non-invasive approaches: colorimetry and X-ray radiography. The obtained results show that the amount of silver NPs can be successfully determined from the luminosity and global color changes of the surface of the foams, as well as from the X-ray attenuance.
Enhanced Tensile Properties of Multi-Walled Carbon Nanotubes Filled Polyamide 6 Composites Based on Interface Modification and Reactive Extrusion
Authors: Park Min , Jang Ji-un , Park Jong Hyuk , Yu Jaesang , Kim Seong Yun
Published: April 2020

To induce uniform dispersion and excellent interfacial properties, we adopted a strategy of combining both polyamide 6 (PA6) grafting for multi-walled carbon nanotubes (MWCNTs) and reactive extrusion of PA6 matrix, based on anionic ring-opening polymerization of ε-caprolactam (CL). Compared to –COOH and –NCO treatments of MWCNTs, enhanced MWCNT dispersion and tensile properties of the composites were achieved using the applied strategy, and the tensile strength and modulus of the PA6-grafted MWCNT-filled PA6 composites were 5.3% and 20.5% higher than those of the purified MWCNT-filled PA6 composites, respectively. In addition, they were almost similar to the theoretical ones calculated by the modified Mori–Tanaka method (MTM) assuming a perfect interface, indicating that the tensile properties of MWCNT-filled PA6 composites can be optimized by PA6 grafting and reactive extrusion based on the anionic ring-opening polymerization of CL due to uniform MWCNT dispersion and excellent interfacial property.
Colorimetric Visualization Using Polymeric Core–Shell Nanoparticles: Enhanced Sensitivity for Formaldehyde Gas Sensors
Authors: Park Jae Jung , Kim Yongsoo , Lee Chanmin , Kook Jun-Won , Kim Donghyun , Kim Jung-Hyun , Hwang Ki-Seob , Lee Jun-Young
Published: April 2020

Although equipment-based gas sensor systems (e.g., high-performance liquid chromatography) have been widely applied for formaldehyde gas detection, pre-treatment and expensive instrumentation are required. To overcome these disadvantages, we developed a colorimetric sensor based on polymer-based core–shell nanoparticles (PCSNPs), which are inexpensive, stable, and exhibit enhanced selectivity. Spherical and uniform poly(styrene-co-maleic anhydride) (PSMA)/polyethyleneimine (PEI) core–shell nanoparticles were prepared and then impregnated with Methyl Red (MR), Bromocresol Purple (BCP), or 4-nitrophenol (4-NP) to construct colorimetric sensors for formaldehyde gas. The intrinsic properties of these dyes were maintained when introduced into the PCSNPs. In the presence of formaldehyde, the MR, BCP, and 4-NP colorimetric sensors changed to yellow, red, and gray, respectively. The colorimetric response was maximized at a PEI/PSMA ratio of four, likely owing to the high content of amine groups. Effective formaldehyde gas detection was achieved at a relative humidity of 30% using the MR colorimetric sensor, which exhibited a large color change (92%) in 1 min. Advantageously, this stable sensor allowed sensitive and rapid naked-eye detection of low formaldehyde concentrations (0.5 ppm). Hence, this approach is promising for real-time formaldehyde gas visualization and can also be adapted to other colorimetric gas sensor systems to improve sensitivity and simplicity.
Bi-Functional Composting the Sulfonic Acid Based Proton Exchange Membrane for High Temperature Fuel Cell Application
Authors: Xu Guoxiao , Zou Juan , Guo Zhu , Li Jing , Ma Liying , Li Ying , Cai Weiwei
Published: April 2020

Although sulfonic acid (SA)-based proton-exchange membranes (PEMs) dominate fuel cell applications at low temperature, while sulfonation on polymers would strongly decay the mechanical stability limit the applicable at elevated temperatures due to the strong dependence of proton conduction of SA on water. For the purpose of bifunctionally improving mechanical property and high-temperature performance, Nafion membrane, which is a commercial SA-based PEM, is composited with fabricated silica nanofibers with a three-dimensional network structure via electrospinning by considering the excellent water retention capacity of silica. The proton conductivity of the silica nanofiber–Nafion composite membrane at 110 °C is therefore almost doubled compared with that of a pristine Nafion membrane, while the mechanical stability of the composite Nafion membrane is enhanced by 44%. As a result, the fuel cell performance of the silica nanofiber-Nafion composite membrane measured at high temperature and low humidity is improved by 38%.
An Integrated High Throughput Experimentation/Predictive QSAR Modeling Approach to ansa-Zirconocene Catalysts for Isotactic Polypropylene
Authors: Ehm Christian , Vittoria Antonio , Goryunov Georgy P. , Izmer Vyatcheslav V. , Kononovich Dmitry S. , Samsonov Oleg V. , Di Girolamo Rocco , Budzelaar Peter H. M. , Voskoboynikov Alexander Z. , Busico Vincenzo , Uborsky Dmitry V. , Cipullo Roberta
Published: April 2020

Compared to heterogenous Ziegler–Natta systems (ZNS), ansa-metallocene catalysts for the industrial production of isotactic polypropylene feature a higher cost-to-performance balance. In particular, the C2-symmetric bis(indenyl) ansa-zirconocenes disclosed in the 1990s are complex to prepare, less stereo- and/or regioselective than ZNS, and lose performance at practical application temperatures. The golden era of these complexes, though, was before High Throughput Experimentation (HTE) could contribute significantly to their evolution. Herein, we illustrate a Quantitative Structure – Activity Relationship (QSAR) model trained on a robust and highly accurate HTE database. The clear-box QSAR model utilizes, in particular, a limited number of chemically intuitive 3D geometric descriptors that screen various regions of space in and around the catalytic pocket in a modular way thus enabling to quantify individual substituent contributions. The main focus of the paper is on the methodology, which should be of rather broad applicability in molecular organometallic catalysis. Then again, it is worth emphasizing that the specific application reported here led us to identify in a comparatively short time novel zirconocene catalysts rivaling or even outperforming all previous homologues which strongly indicates that the metallocene story is not over yet.
Enhancement of Oil Palm Waste Nanoparticles on the Properties and Characterization of Hybrid Plywood Biocomposites
Authors: Nuryawan Arif , Abdullah C. , Hazwan Che , Olaiya N. , Yahya Esam , Risnasari Iwan , Masruchin Nanang , Baharudin M. , Khalid Hasmawi , Abdul Khalil H.
Published: April 2020

Using oil palm trunk (OPT) layered with empty fruit bunch (EFB), so-called hybrid plywood enhanced with palm oil ash nanoparticles, with phenol-formaldehyde (PF) resin as a binder, was produced in this study. The phenol-formaldehyde (PF) resins filled with different loading of oil palm ash (OPA) nanoparticles were prepared and used as glue for layers of the oil palm trunk (OPT) veneer and empty fruit bunch fibre mat. The resulting hybrid plywood produced was characterised. The physical, mechanical, thermal, and morphological properties of the hybrid plywood panels were investigated. The results obtained showed that the presence of OPA nanoparticles significantly affected the physical, mechanical, and thermal properties of the plywood panels. Significant improvements in dimension from water absorption and thickness swelling experiments were obtained for the plywood panels with the highest OPA nanoparticles loading in PF resin. The mechanical properties indicated that plywood composites showed improvement in flexural, shear, and impact properties until a certain loading of OPA nanoparticles in PF resin. Fracture surface morphology also showed the effectiveness of OPA nanoparticles in the reduction of layer breakage due to force and stress distribution. The thermal stability performance showed that PF filled OPA nanoparticles contributed to the thermal stability of the plywood panels. Therefore, the results obtained in this study showed that OPA nanoparticles certainly improved the characteristic of the hybrid plywood.
A Sacrificial Route for Soft Porous Polymers Synthesized via Frontal Photo-Polymerization
Authors: Turani-i-Belloto Alexandre , Brunet Thomas , Khaldi Alexandre , Leng Jacques
Published: April 2020

Within the very large range of porous polymers and a related immense scope of applications, we investigate here a specific route to design soft porous polymers with controlled porosity: we use aqueous-based formulations of oligomers with mineral particles which are solidified into a hydrogel upon photo-polymerization; the embedded particles are then chemically etched and the hydrogel is dried to end up with a soft porous polymeric scaffold with micron-scale porosity. Morphological and physical features of the porous polymers are measured and we demonstrate that the porosity of the final material is primarily determined by the amount of initially dispersed sacrificial particles. In addition, the liquid formulations we use to start with are convenient for a variety of material forming techniques such as microfluidics, embossing, etc., which lead to many different morphologies (monoliths, spherical particles, patterned substrates) based on the same initial material.