bluuebunny/crossref_metadata_2025 huggingface dataset:
Alpha-5 Integrin Mediates Simvastatin-Induced Osteogenesis of Bone Marrow Mesenchymal Stem Cells
Authors: Shao Pei-Lin , Wu Shun-Cheng , Lin Zih-Yin , Ho Mei-Ling , Chen Chung-Hwan , Wang Chau-Zen
Published: January 2019

Simvastatin (SVS) promotes the osteogenic differentiation of mesenchymal stem cells (MSCs) and has been studied for MSC-based bone regeneration. However, the mechanism underlying SVS-induced osteogenesis is not well understood. We hypothesize that α5 integrin mediates SVS-induced osteogenic differentiation. Bone marrow MSCs (BMSCs) derived from BALB/C mice, referred to as D1 cells, were used. Alizarin red S (calcium deposition) and alkaline phosphatase (ALP) staining were used to evaluate SVS-induced osteogenesis of D1 cells. The mRNA expression levels of α5 integrin and osteogenic marker genes (bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (Runx2), collagen type I, ALP and osteocalcin (OC)) were detected using quantitative real-time PCR. Surface-expressed α5 integrin was detected using flow cytometry analysis. Protein expression levels of α5 integrin and phosphorylated focal adhesion kinase (p-FAK), which is downstream of α5 integrin, were detected using Western blotting. siRNA was used to deplete the expression of α5 integrin in D1 cells. The results showed that SVS dose-dependently enhanced the gene expression levels of osteogenic marker genes as well as subsequent ALP activity and calcium deposition in D1 cells. Upregulated p-FAK was accompanied by an increased protein expression level of α5 integrin after SVS treatment. Surface-expressed α5 integrin was also upregulated after SVS treatment. Depletion of α5 integrin expression significantly suppressed SVS-induced osteogenic gene expression levels, ALP activity, and calcium deposition in D1 cells. These results identify a critical role of α5 integrin in SVS-induced osteogenic differentiation of BMSCs, which may suggest a therapeutic strategy to modulate α5 integrin/FAK signaling to promote MSC-based bone regeneration.
Acknowledgement to Reviewers of Inventions in 2018
Authors:   Inventions Editorial Office
Published: January 2019

Rigorous peer-review is the corner-stone of high-quality academic publishing [...]
Prognostic Role of Circulating miRNAs in Early-Stage Non-Small Cell Lung Cancer
Authors: Ulivi Paola , Petracci Elisabetta , Marisi Giorgia , Baglivo Sara , Chiari Rita , Billi Monia , Canale Matteo , Pasini Luigi , Racanicchi Serena , Vagheggini Alessandro , Delmonte Angelo , Mariotti Marita , Ludovini Vienna , Bonafè Massimiliano , Crinò Lucio , Grignani Francesco
Published: January 2019

Non-small cell lung cancer (NSCLC) is the primary cause of cancer-related death worldwide, with a low 5-year survival rate even in fully resected early-stage disease. Novel biomarkers to identify patients at higher risk of relapse are needed. We studied the prognostic value of 84 circulating microRNAs (miRNAs) in 182 patients with resected early-stage NSCLC (99 adenocarcinoma (ADC), 83 squamous cell carcinoma (SCC)) from whom peripheral blood samples were collected pre-surgery. miRNA expression was analyzed in relation to disease-free survival (DFS) and overall survival (OS). In univariable analyses, five miRNAs (miR-26a-5p, miR-126-3p, miR-130b-3p, miR-205-5p, and miR-21-5p) were significantly associated with DFS in SCC, and four (miR-130b-3p, miR-26a-5p, miR-126-3p, and miR-205-5p) remained significantly associated with OS. In ADC, miR-222-3p, miR-22-3p, and mir-93-5p were significantly associated with DFS, miR-22-3p remaining significant for OS. Given the high-dimensionality of the dataset, multivariable models were obtained using a regularized Cox regression including all miRNAs and clinical covariates. After adjustment for disease stage, only miR-126-3p showed an independent prognostic role, with higher values associated with longer DFS in SCC patients. With regard to ADC and OS, no miRNA remained significant in multivariable analysis. Further investigation into the role of miR-126 as a prognostic marker in early-stage NSCLC is warranted.
Application of Cold Wire Gas Metal Arc Welding for Narrow Gap Welding (NGW) of High Strength Low Alloy Steel
Authors: Ribeiro Rafael , Assunção Paulo , Dos Santos Emanuel , Filho Ademir , Braga Eduardo , Gerlich Adrian
Published: January 2019

Narrow gap welding is a prevalent technique used to decrease the volume of molten metal and heat required to fill a joint. Consequently, deleterious effects such as distortion and residual stresses may be reduced. One of the fields where narrow groove welding is most employed is pipeline welding where misalignment, productivity and mechanical properties are critical to a successful final assemblage of pipes. This work reports the feasibility of joining pipe sections with 4 mm-wide narrow gaps machined from API X80 linepipe using cold wire gas metal arc welding. Joints were manufactured using the standard gas metal arc welding and the cold wire gas metal arc welding processes, where high speed imaging, and voltage and current monitoring were used to study the arc dynamic features. Standard metallographic procedures were used to study sidewall penetration, and the evolution of the heat affected zone during welding. It was found that cold wire injection stabilizes the arc wandering, decreasing sidewall penetration while almost doubling deposition. However, this also decreases penetration, and incomplete penetration was found in the cold wire specimens as a drawback. However, adjusting the groove geometry or changing the welding parameters would resolve this penetration issue.
Microstructure and Enhanced Properties of Copper-Vanadium Nanocomposites Obtained by Powder Metallurgy
Authors: Wang Yong , Wang Jinguo , Zou Haohao , Wang Yutong , Ran Xu
Published: January 2019

Cu-2.4 wt.%V nanocomposite has been prepared by mechanical alloy and vacuum hot-pressed sintering technology. The composites were sintered at 800 °C, 850 °C, 900 °C, and 950 °C respectively. The microstructure and properties of composites were investigated. The results show that the Cu-2.4 wt.%V composite presents high strength and high electrical conductivity. The composite sintered at 900 °C has a microhardness of 205 HV, a yield strength of 404.41 MPa, and an electrical conductivity of 79.5% International Annealed Copper Standard (IACS); the microhardness and yield strength reduce gradually with the increasing consolidation temperature, which is mainly due to the growth of copper grain size. After sintering, copper grain size and V nanoparticle both maintain in nanoscale; the strengthening mechanism is related to grain boundary strengthening and dispersion strengthening, while the grain boundary strengthening mechanism plays the most important role. This study indicates that the addition of small amounts of V element could enhance the copper matrix markedly with the little sacrifice of electrical conductivity.
Dissolvable Polyvinyl-Alcohol Film, a Time-Barrier to Modulate Sample Flow in a 3D-Printed Holder for Capillary Flow Paper Diagnostics
Authors: Harpaz Dorin , Axelrod Tim , Yitian Alicia , Eltzov Evgeni , Marks Robert , Tok Alfred
Published: January 2019

Integrating a dissolvable membrane into a sensor allows the control of sample flow, location and duration in critical areas. These time-barrier films stop the flow of samples until the membrane has dissolved, thus, for example, allowing increased exposure time between immunoreagents for the formation of greater numbers of immuno-complexes, ensuring higher sensitivity, reactivity, and helping to reduce false-positive signals. In this study, dissolvable polyvinyl alcohol (PVA) films are used in a 3D-printed sensor holder, which enables film integration without the use of glue. PVA is a synthetic hydrophilic linear polymer, its solubility is dependent on its molecular weight and degree of hydrolysis. Three types of PVAs films were tested herein: (1) PVA 1-Mw: 30–70 K, 87–90% hydrolyzed; (2) PVA 2-Mw: 31–50 K, 98–99% hydrolyzed and (3) PVA 3-Mw: 89–98 K, >99% hydrolyzed. The films were exposed to water in (1) the novel 3D-printed holder and (2) directly immersed into a water droplet. After comparing the time taken to dissolve PVA 1–3 films, PVA 1 films of 5–20% (w/v) are found to be most suitable as time barrier films, due to their optimal dissolution times and physical properties for integration into the customized 3D-printed holder.
Enhancing the Dyeability of Polyimide Fibers with the Assistance of Swelling Agents
Authors: Shao Dongyan , Xu Changhai , Wang Hongbo , Du Jinmei
Published: January 2019

Polyimide (PI) fibers have outstanding thermal stability and mechanical properties, but are difficult to dye with disperse and basic dyes. In this work, it was proposed to use N-methylformanilide (MFA), phenoxyisopropanol (PIP), and acetophenone (AP) as swelling agents to enhance the dyeability of PI fibers. The PI fibers treated with swelling agents were characterized by thermal gravimetric analysis, scanning electronic microscopy, tensile testing, and crystalline analysis. It was found that the swelling agents penetrated into the PI fibers in amounts greater than 10% (pertaining to the weight of PI fibers). The swelling agents did not really swell the PI fibers, but broke the interaction forces between the PI macromolecules. With the assistance of swelling agent, the PI fibers could be dyed with disperse and basic dyes in strong color strengths. AP exhibited the best performance for enhancing the dyeability of PI fibers, followed by MFA and PIP. The dyed PI fibers were found to have good colorfastness to washing.
Using Fluorescence Quenching Titration to Determine the Orientation of a Model Transmembrane Protein in Mimic Membranes
Authors: Huang Haihong , Ge Baosheng , Zhang Shuai , Li Jiqiang , Sun Chenghao , Yue Tongtao , Huang Fang
Published: January 2019

After synthesis of transmembrane proteins (TMPs), they are transferred and inserted into plasma membranes to play biological functions. Crucially, orientation of TMPs in membranes determines whether they have biological activities. In cellular environments, a number of cofactors, such as translocon, can assist TMPs to be inserted into membranes in defined orientations. During in vitro reconstitution of TMPs with mimic membranes, both insertion and orientation of TMPs are primarily determined by interactions with the membrane. Yet the knowledge is limited, hindering the in vitro applications of TMPs. Here, we take Bacteriorhodopsin (bR) as a model TMP, using fluorescence quenching titration experiment to identify orientation of bR in mimic membranes, examining effects of a number of factors, including lipid composition, pH value, ionic strength and membrane curvature. The most effective determinant is the lipid type, which modulates insertion and orientation of bR in membranes by changing the membrane surface charge and the membrane fluidity. Both the pH value and the ionic strength play secondary roles by tuning the nature of the electrostatic interaction. The membrane curvature was found to have a minor effect on orientation of bR in membranes. By comparing orientations of bR in folded and unfolded states, no obvious change was observed, informing that nascent proteins could be inserted into membranes in defined orientations before folding into the native state inside the membrane.
Drug Release Profiles and Disintegration Properties of Pectin Films
Authors: Murata Yoshifumi , Maida Chieko , Kofuji Kyoko
Published: January 2019

We assessed the disintegration profiles of the film dosage forms (FDs) prepared using pectin by measuring the amount of pectin dissolved from the films in a limited amount of aqueous medium. Furthermore, we used miconazole and dexamethasone as standard drugs and investigated the relationship between the disintegration rate of the FDs and the rate of drug release. We used two types of pectin in this study to develop thin films with a thickness of approximately 25–35 μm. The FDs gradually disintegrated in the aqueous medium, and the disintegration profile of the FDs differed depending on the types of pectin. In addition, the rate of disintegration of the film matrix affected the dissolution rate of the drug incorporated into the FD. Thus, our results show that FDs prepared using pectin are beneficial because of their high solubility in a limited amount of medium, and the rate of drug release from the FDs can be regulated by selecting a specific type of pectin or by altering the concentration of the film base.
Biological Performance of Electrospun Polymer Fibres
Authors: Hall Barrientos Ivan Joseph , MacKenzie Graeme R. , Wilson Clive G. , Lamprou Dimitrios A. , Coats Paul
Published: January 2019

The evaluation of biological responses to polymeric scaffolds are important, given that the ideal scaffold should be biocompatible, biodegradable, promote cell adhesion and aid cell proliferation. The primary goal of this research was to measure the biological responses of cells against various polymeric and collagen electrospun scaffolds (polycaprolactone (PCL) and polylactic acid (PLA) polymers: PCL–drug, PCL–collagen–drug, PLA–drug and PLA–collagen–drug); cell proliferation was measured with a cell adhesion assay and cell viability using 5-bromo-2′-deoxyuridine (BrdU) and resazurin assays. The results demonstrated that there is a distinct lack of growth of cells against any irgasan (IRG) loaded scaffolds and far greater adhesion of cells against levofloxacin (LEVO) loaded scaffolds. Fourteen-day studies revealed a significant increase in cell growth after a 7-day period. The addition of collagen in the formulations did not promote greater cell adhesion. Cell viability studies revealed the levels of IRG used in scaffolds were toxic to cells, with the concentration used 475 times higher than the EC50 value for IRG. It was concluded that the negatively charged carboxylic acid group found in LEVO is attracting positively charged fibronectin, which in turn is attracting the cell to adhere to the adsorbed proteins on the surface of the scaffold. Overall, the biological studies examined in this paper are valuable as preliminary data for potential further studies into more complex aspects of cell behaviour with polymeric scaffolds.
On the Corrosion Mechanism of CO2 Transport Pipeline Steel Caused by Condensate: Synergistic Effects of NO2 and SO2
Authors: Quynh Hoa Le , Baessler Ralph , Bettge Dirk
Published: January 2019

To study the effects of condensed acid liquid, hereafter referred to as condensate, on the CO2 transport pipeline steels, gas mixtures containing a varying concentration of H2O, O2, NO2, and SO2, were proposed and resulted in the condensate containing H2SO4 and HNO3 with the pH ranging from 0.5 to 2.5. By exposing the pipeline steel to the synthetic condensate with different concentration of acidic components, the corrosion kinetic is significantly changed. Reaction kinetic was studied using electrochemical methods coupled with water analysis and compared with surface analysis (scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffractometry (XRD)) of corroded coupons. The results showed that, although the condensation of NO2 in the form of HNO3 causes faster general corrosion rate, it is the condensation of SO2 in the form of H2SO4 or the combination of SO2 and NO2 that may cause much more severe problems in the form of localized and pitting corrosions. The resulting corrosion forms were depended on the chemical nature of acids and their concentration at the same investigated pH. The effects of changing CO2 flow rate and renewing condensate on pitting corrosion were further studied.
Dynamics and Kinetics of Cupric Ion Removal from Wastewaters by Tunisian Solid Crude Olive-Oil Waste
Authors: Khiari Besma , Wakkel Manel , Abdelmoumen Souhir , Jeguirim Mejdi
Published: January 2019

The present paper aims to develop a low cost, efficient, and environmentally-friendly process to purify (industrial) waters contaminated by copper by the use of oil mill wastes, through kinetic, thermodynamic, and equilibrium investigations. To do so, the raw adsorbent was characterized using different analytical techniques including X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Then, the interaction between copper and olive residues were examined during batch adsorption tests at various operating parameters, such as pH, initial concentration, contact time, and particle size. Kinetic data were best fitted with Broeurs-Sotolongo kinetic model. Additionally, it was found that film and intraparticle diffusion steps controlled simultaneously the mass transfer of copper onto olive mill solid waste. Among the eight tested models, Broeurs-Sotolongo isotherm suited the most the sorption, with regards to the function errors analysis. It was deduced that the adsorption of copper does not involve chemical bonds with high energy which allows easier regeneration steps and higher number of biosorbent regeneration cycles without any need for applying high temperature in the desorption reaction systems. The adsorption capacity (18.93 mg/g) calculated on the basis of this model was close to the experimental value (18.4 mg/g) but more interestingly it brought up that 50% of the generated amounts of olive wastes in Tunisia could eliminate 1.84 kTons of copper from industrial waters.
The Influence of Heat and Mechanical Treatment of Concrete Rubble on the Properties of Recycled Aggregate Concrete
Authors: Pawluczuk Edyta , Kalinowska-Wichrowska Katarzyna , Bołtryk Michał , Jiménez José , Fernández José
Published: January 2019

Concrete is a building material commonly used for ages. Therefore, in the result of repairs or demolition of building structures, large amounts of concrete rubble are created, which requires appropriate management. The aim of the realized research was to determine the influence of heat and mechanical treatment of concrete rubble on the properties of recycled aggregate concrete. The research experiment included 12 series, with three variables: X1—roasting temperature (300, 600, 900 °C), X2—time of mechanical treatment (5, 10, 15 min), X3—content of coarse recycled aggregates (20, 40, 60% by volume). Two additional series containing recycled aggregate without treatment and natural aggregate were also prepared. Established properties of individual aggregates have confirmed a positive effect of thermo-mechanical treatment. Then, based on the results of compressive strength, flexural strength, Young’s modulus, volumetric density, water absorption, water permeability and capillarity, the most favourable parameters of heat and mechanical treatment of concrete were determined. The test results showed that appropriate treatment of concrete rubble allows to obtain high-quality coarse aggregate and valuable fine fraction. This was also confirmed by the macro- and microscopic observations of the aggregate and separated cement paste. Works realized on the concrete recycling method resulted in obtaining a patent PAT.229887.
Classification of Warped Product Submanifolds in Kenmotsu Space Forms Admitting Gradient Ricci Solitons
Authors: Alkhaldi Ali H. , Ali Akram
Published: January 2019

The purpose of this article is to obtain geometric conditions in terms of gradient Ricci curvature, both necessary and sufficient, for a warped product semi-slant in a Kenmotsu space form, to be either CR-warped product or simply a Riemannian product manifold when a basic inequality become equality. The next purpose of this paper to find the necessary condition admitting gradient Ricci soliton, that the warped product semi-slant submanifold of Kenmotsu space form, is an Einstein warped product. We also discuss some obstructions to these constructions in more detail.
A Meshless Method for Burgers’ Equation Using Multiquadric Radial Basis Functions With a Lie-Group Integrator
Authors: Seydaoğlu Muaz
Published: January 2019

An efficient technique is proposed to solve the one-dimensional Burgers’ equation based on multiquadric radial basis function (MQ-RBF) for space approximation and a Lie-Group scheme for time integration. The comparisons of the numerical results obtained for different values of kinematic viscosity are made with the exact solutions and the reported results to demonstrate the efficiency and accuracy of the algorithm. It is shown that the numerical solutions concur with existing results and the proposed algorithm is efficient and can be easily implemented.
Numerical Simulation of Rotor–Wing Transient Interaction for a Tiltrotor in the Transition Mode
Authors: Wu Zhenlong , Li Can , Cao Yihua
Published: January 2019

Tiltrotor aerodynamic interaction, especially in the transition mode, is a necessary consideration for tiltrotor aerodynamics, and structural design and optimization. Previous studies have paid much attention to the helicopter mode. However, due to the substantial complexity of the problem, only a small amount of work on the transition mode has been done so far. In this paper, the rotor–wing aerodynamic interaction of a scaled V-22 Osprey tiltrotor, both in the helicopter and transition modes, are studied by computational fluid dynamics (CFD) numerical simulation. The flow field is discretized via the chimera mesh technique and then solved with the Reynolds-averaged Navier–Stokes (RANS) equations. The rotational acceleration of the rotor is considered as a source term added on the right side of the momentum equation of the RANS equations. Both a quasi-steady and a fully transient method are employed to simulate the tilt motion of the rotor in the transition mode. Both qualitative and quantitative results are presented and discussed on the aerodynamic forces, flow physics, and mechanisms. The applicability of the extensively used quasi-steady method for rotor tilt simulation is revealed.
Preparation and Characterization of Gelatin and Antioxidant Peptides from Gelatin Hydrolysate of Skipjack Tuna (Katsuwonus pelamis) Bone Stimulated by in vitro Gastrointestinal Digestion
Authors: Yang Xiu-Rong , Zhao Yu-Qin , Qiu Yi-Ting , Chi Chang-Feng , Wang Bin
Published: January 2019

In China, a large amount of fish bones are produced during the processing of tuna cans production. For full use of those by-products, gelatin (STB-G) with a yield of 6.37 ± 0.64% was extracted from skipjack tuna (Katsuwonus pelamis) bone using water at 60 °C for 8 h. Amino acid analysis showed that STB-G contained Gly (340.3 residues/1000 residues) as the major amino acid and its imino acid content was 177.3 residues/1000 residues. Amino acid composition, SDS-PAGE, and Fourier transform infrared (FTIR) spectrum investigations confirmed that the physicochemical properties of STB-G were similar to those of type I collagen from skipjack tuna bone (STB-C), but partial high molecular weight components of STB-G were degraded during the extraction process, which induced that the gelatin was easier to be hydrolyzed by protease than mammalian gelatins and was suitable for preparation of hydrolysate. Therefore, STB-G was hydrolyzed under in vitro gastrointestinal digestion (pepsin-trypsin system) and five antioxidant peptides were purified from the resulted hydrolysate (STB-GH) and identified as GPDGR, GADIVA, GAPGPQMV, AGPK, and GAEGFIF, respectively. Among the gelatin hydrolysate, fractions, and isolated peptides, GADIVA and GAEGFIF exhibited the strongest scavenging activities on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical (EC50 0.57 and 0.30 mg/mL), hydroxyl radical (EC50 0.25 and 0.32 mg/mL), superoxide anion radical (EC50 0.52 and 0.48 mg/mL), and 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical (EC50 0.41 and 0.21 mg/mL). Moreover, GADIVA and GAEGFIF showed a high inhibiting ability on lipid peroxidation in a linoleic acid model system. The strong activities of five isolated peptides profited by their small molecular sizes and the antioxidant amino acid residues in their sequences. These results suggested that five isolated peptides (STP1–STP5), especially GADIVA and GAEGFIF, might serve as potential antioxidants applied in health food industries.
Competence for Natural Transformation Is Common among Clinical Strains of Resistant Acinetobacter spp.
Authors: Domingues Sara , Rosário Natasha , Cândido Ângela , Neto Daniela , Nielsen Kaare M. , Da Silva Gabriela J.
Published: January 2019

Horizontal gene transfer events provide the basis for extensive dissemination of antimicrobial resistance traits between bacterial populations. Conjugation is considered to be the most frequent mechanism behind new resistance acquisitions in clinical pathogens but does not fully explain the resistance patterns seen in some bacterial genera. Gene transfer by natural transformation has been described for numerous clinical isolates, including some Acinetobacter species. The main aim of this study was to determine to what extent clinical, resistant Acinetobacter spp. isolates, express competence for natural transformation. Twenty-two clinical Acinetobacter spp. isolates collected over a 16-year time period, from five different geographical separated and/or distinct Portuguese Hospitals were tested for natural transformability. Fourteen isolates, including 11 A. baumannii, 2 A. nosocomialis and 1 Acinetobacter sp., were identified as competent on semisolid media facilitating surface-motility. Competent Acinetobacter isolates were found in all the hospitals tested. Furthermore, osmolarity was shown to influence the uptake of exogenous DNA by competent A. baumannii A118. Our study demonstrates that natural competence is common among clinical isolates of Acinetobacter spp., and hence likely an important trait for resistance acquisition.
Modification of Immobilized Titanium Dioxide Nanostructures by Argon Plasma for Photocatalytic Removal of Organic Dyes
Authors: Khaledian Hamid Reza , Zolfaghari Pezhman , Elhami Vahide , Aghbolaghy Mostafa , Khorram Sirous , Karimi Afzal , Khataee Alireza
Published: January 2019

The aim of this study was to modify surface properties of immobilized rutile TiO2 using Argon cold plasma treatment and to evaluate the performance of the catalyst in photocatalytic elimination of synthetic dyes in UV/TiO2/H2O2 process. The surface-modified TiO2 was characterized by XRD, EDX, SEM, UV-DRS and XPS analyses. Response surface methodology was adopted to achieve high catalyst efficiency by evaluating the effect of two main independent cold plasma treatment parameters (exposure time and pressure) on surface modification of the catalyst. The increase of the plasma operation pressure led to higher decolorization percentage, while the increase of plasma exposure time decreased the decolorization efficiency. RSM methodology predicted optimum plasma treatment conditions to be 0.78 Torr and 21 min of exposure time, which resulted in decolorization of 10 mg/L solution of the malachite green solution by 94.94% in 30 min. The plasma treatment decreased the oxygen to titanium ratio and caused oxygen vacancy on the surface of the catalyst, resulting in the superior performance of the plasma-treated catalyst. Pseudo first-order kinetic rate constant for the plasma-treated catalyst was 4.28 and 2.03 times higher than the rate constant for the non-treated photocatalyst in decolorization of aqueous solutions of malachite green and crystal violet, respectively.
Secalonic Acid-F, a Novel Mycotoxin, Represses the Progression of Hepatocellular Carcinoma via MARCH1 Regulation of the PI3K/AKT/β-catenin Signaling Pathway
Authors: Xie Lulu , Li Minjing , Liu Desheng , Wang Xia , Wang Peiyuan , Dai Hanhan , Yang Wei , Liu Wei , Hu Xuemei , Zhao Mingdong
Published: January 2019

Liver cancer is a very common and significant health problem. Therefore, powerful molecular targeting agents are urgently needed. Previously, we demonstrated that secalonic acid-F (SAF) suppresses the growth of hepatocellular carcinoma (HCC) cells (HepG2), but the other anticancer biological functions and the underlying mechanism of SAF on HCC are unknown. In this study, we found that SAF, which was isolated from a fungal strain in our lab identified as Aspergillus aculeatus, could inhibit the progression of hepatocellular carcinoma by targeting MARCH1, which regulates the PI3K/AKT/β-catenin and antiapoptotic Mcl-1/Bcl-2 signaling cascades. First, we confirmed that SAF reduced the proliferation and colony formation of HCC cell lines (HepG2 and Hep3B), promoted cell apoptosis, and inhibited the cell cycle in HepG2 and Hep3B cells in a dose-dependent manner. In addition, the migration and invasion of HepG2 and Hep3B cells treated with SAF were significantly suppressed. Western blot analysis showed that the level of MARCH1 was downregulated by pretreatment with SAF through the regulation of the PI3K/AKT/β-catenin signaling pathways. Moreover, knockdown of MARCH1 by small interfering RNAs (siRNAs) targeting MARCH1 also suppressed the proliferation, colony formation, migration, and invasion as well as increased the apoptotic rate of HepG2 and Hep3B cells. These data confirmed that the downregulation of MARCH1 could inhibit the progression of hepatocellular carcinoma and that the mechanism may be via PI3K/AKT/β-catenin inactivation as well as the downregulation of the antiapoptotic Mcl-1/Bcl-2. In vivo, the downregulation of MARCH1 by treatment with SAF markedly inhibited tumor growth, suggesting that SAF partly blocks MARCH1 and further regulates the PI3K/AKT/β-catenin and antiapoptosis Mcl-1/Bcl-2 signaling cascade in the HCC nude mouse model. Additionally, the apparent diffusion coefficient (ADC) values, derived from magnetic resonance imaging (MRI), were increased in tumors after SAF treatment in a mouse model. Taken together, our findings suggest that MARCH1 is a potential molecular target for HCC treatment and that SAF is a promising agent targeting MARCH1 to treat liver cancer patients.
Biotransformed Metabolites of the Hop Prenylflavanone Isoxanthohumol
Authors: Kim Hyun Jung , Yim Soon-Ho , Han Fubo , Kang Bok Yun , Choi Hyun Jin , Jung Da-Woon , Williams Darren R. , Gustafson Kirk R. , Kennelly Edward J. , Lee Ik-Soo
Published: January 2019

A metabolic conversion study on microbes is known as one of the most useful tools to predict the xenobiotic metabolism of organic compounds in mammalian systems. The microbial biotransformation of isoxanthohumol (1), a major hop prenylflavanone in beer, has resulted in the production of three diastereomeric pairs of oxygenated metabolites (2–7). The microbial metabolites of 1 were formed by epoxidation or hydroxylation of the prenyl group, and HPLC, NMR, and CD analyses revealed that all of the products were diastereomeric pairs composed of (2S)- and (2R)- isomers. The structures of these metabolic compounds were elucidated to be (2S,2″S)- and (2R,2″S)-4′-hydroxy-5-methoxy-7,8-(2,2-dimethyl-3-hydroxy-2,3-dihydro-4H-pyrano)-flavanones (2 and 3), (2S)- and (2R)-7,4′-dihydroxy-5-methoxy-8-(2,3-dihydroxy-3-methylbutyl)-flavanones (4 and 5) which were new oxygenated derivatives, along with (2R)- and (2S)-4′-hydroxy-5-methoxy-2″-(1-hydroxy-1-methylethyl)dihydrofuro[2,3-h]flavanones (6 and 7) on the basis of spectroscopic data. These results could contribute to understanding the metabolic fates of the major beer prenylflavanone isoxanthohumol that occur in mammalian system.
Developing Novel G-Quadruplex Ligands: From Interaction with Nucleic Acids to Interfering with Nucleic Acid–Protein Interaction
Authors: Sun Zhi-Yin , Wang Xiao-Na , Cheng Sui-Qi , Su Xiao-Xuan , Ou Tian-Miao
Published: January 2019

G-quadruplex is a special secondary structure of nucleic acids in guanine-rich sequences of genome. G-quadruplexes have been proved to be involved in the regulation of replication, DNA damage repair, and transcription and translation of oncogenes or other cancer-related genes. Therefore, targeting G-quadruplexes has become a novel promising anti-tumor strategy. Different kinds of small molecules targeting the G-quadruplexes have been designed, synthesized, and identified as potential anti-tumor agents, including molecules directly bind to the G-quadruplex and molecules interfering with the binding between the G-quadruplex structures and related binding proteins. This review will explore the feasibility of G-quadruplex ligands acting as anti-tumor drugs, from basis to application. Meanwhile, since helicase is the most well-defined G-quadruplex-related protein, the most extensive research on the relationship between helicase and G-quadruplexes, and its meaning in drug design, is emphasized.
Proanthocyanidins Protect against β-Hydroxybutyrate-Induced Oxidative Damage in Bovine Endometrial Cells
Authors: Cheng Xi , Yang Shuhua , Xu Chuang , Li Lanzhi , Zhang Yi , Guo Yang , Zhang Cai , Li Peng , Long Miao , He Jianbin
Published: January 2019

Metabolic diseases, such as ketosis, are closely associated with decreased reproductive performance (such as delayed estrus and decreased pregnancy rate) in dairy cows. The change of β-hydroxybutyrate (BHBA) concentration in dairy cattle is an important mechanism leading to ketosis, and its blood concentration in ketotic cows is always significantly higher than in nonketotic cows. Many studies indicated that BHBA can induce oxidative damage in liver and other organs. Proanthocyanidins (PCs) have gained substantial attention in the last decade as strong antioxidative substances. This study aimed to demonstrate a protective effect of PCs against BHBA-induced oxidative stress damage in bovine endometrial (BEND) cells by activating the nuclear erythroid2-related factor2 (Nrf2) signaling pathway. Our research show that PCs could significantly increase activities of catalase (CAT) and glutathione peroxidase (GSH-PX), glutathione (GSH) content, and antioxidant capacity (T-AOC), while significantly decreasing malondialdehyde (MDA) content in BEND cells. Both mRNA and protein expression levels of Nrf2 were significantly increased in BEND cells, and glutamate–cysteine ligase catalytic subunit (GCLC), heme oxygenase 1 (HO-1), manganese superoxide dismutase (Mn-SOD), and NAD(P)H quinone dehydrogenase 1 (NQO-1) were also significantly increased. These results indicate that PCs can antagonize BHBA-induced oxidative damage by activating the Nrf2 signaling pathway to exert an antioxidant effect.
Induction of Cell Death in Human A549 Cells Using 3-(Quinoxaline-3-yl) Prop-2-ynyl Methanosulphonate and 3-(Quinoxaline-3-yl) Prop-2-yn-1-ol
Authors: Sibiya Mixo Aunny , Raphoko Lerato , Mangokoana Dikgale , Makola Raymond , Nxumalo Winston , Matsebatlela Thabe Moses
Published: January 2019

Despite major advancements in the development of various chemotherapeutic agents, treatment for lung cancer remains costly, ineffective, toxic to normal non-cancerous cells, and still hampered by a high level of remissions. A novel cohort of quinoxaline derivatives designed to possess a wide spectrum of biological activities was synthesized with promising targeted and selective anticancer drug activity. Hence, this study was aimed at determining in vitro anticancer activity effects of a newly synthesized class of 3-(quinoxaline-3-yl) prop-2-ynyl quinoxaline derivatives on A549 lung cancer cells. An assessment of the quinoxaline derivatives ferric reducing power, free radical scavenging activity, cytotoxic activity, and ability to induce reactive oxygen species (ROS) production was performed using the Ferric Reducing Antioxidant Power (FRAP), 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and 2’,7’-dichlorodihydrofluorescein diacetate (H2DCFDA) assays, respectively. The ability of the quinoxaline derivatives to induce apoptosis in A549 cells was assessed using the Acridine Orange/Ethidium Bromide (AO/EB) and Annexin V-FITC/Dead Cell Assay. Of the four quinoxaline derivatives tested, 3-(quinoxaline-3-yl) prop-2-ynyl methanosulphate (LA-39B) and 3-(quinoxaline-3-yl) prop-2-yn-1-ol (LA-55) displayed a dose-dependent reducing power, free-radical scavenging activity, inhibition of cell viability, and stimulation of ROS production which was accompanied by induction of apoptosis in A549 lung cancer cells. None of the quinoxaline derivatives induced cell death or ROS production in non-cancerous Raw 267.4 macrophage cells. Cytotoxicity was observed in A549 lung cancer, HeLa cervical cancer, and MCF-7 breast cancer cells albeit inhibition was more pronounced in A549 cells. The results of the study suggest that 3-(quinoxaline-3-yl) prop-2-ynyl methanosulphate and 3-(quinoxaline-3-yl) prop-2-yn-1-ol induce apoptotic cell death in A549 lung cancer cells.
A Green-emitting Fluorescent Probe Based on a Benzothiazole Derivative for Imaging Biothiols in Living Cells
Authors: Ma Xiaohua , Hao Yuanqiang , Liu Jiaxiang , Wu Guoguang , Liu Lin
Published: January 2019

A new green-emitting fluorescent probe 1 was developed for biothiol detection. The sensing mechanism was considered to be biothiol-induced cleavage of the 2,4-dinitrobenzene- sulfonate group in probe 1 and resulting inhibition of the probe’s photoinduced electron transfer (PET) process. Probe 1 exhibited favorable properties such as excellent selectivity, highly sensitive (0.12 µM), large Stokes shift (117 nm) and a remarkable turn-on fluorescence signal (148-fold). Furthermore, confocal fluorescence imaging indicated that probe 1 was membrane-permeable and suitable for visualization of biothiols in living A549 cells.
Intake of Sugar-Sweetened Beverages in Adolescents from Troms, Norway—The Tromsø Study: Fit Futures
Authors: Skeie Guri , Sandvær Vårin , Grimnes Guri
Published: January 2019

High intake of sugar-sweetened beverages (SSB) has been associated with weight gain and chronic disease. The objective of this paper was to study the intake of SSB and characteristics associated with SSB intake in adolescents from Troms, Norway. We present results from a cross-sectional analysis from the Tromsø Study: Fit Futures, with 426 female and 444 male students aged 15–17 years (93% participation rate). Descriptive statistics and logistic regression analyses were performed. Among females, 31.8% drank at least one glass of SSB per day on average, compared to 61.0% among males. The adjusted OR (odds ratio) of daily SSB drinking for males vs. females was 3.74 (95% CI (confidence interval) 2.68–5.22). Other dietary habits such as eating snacks, drinking artificially sweetened beverages, fruit juice, and seldom eating breakfast were associated with higher odds for daily SSB drinking, as was daily snuffing. Weight class was not associated with daily SSB drinking. Students in vocational studies, particularly males tended to be more likely to be daily SSB drinkers. The prevalence of participants who on average were daily drinkers was higher than in national studies. We have identified several possible targets for interventions. Clustering of unhealthy behaviours and tendencies to socioeconomic differences are of particular concern.
Use of Dairy and Plant-Derived Lactobacilli as Starters for Cherry Juice Fermentation
Authors: Ricci Annalisa , Cirlini Martina , Maoloni Antonietta , Del Rio Daniele , Calani Luca , Bernini Valentina , Galaverna Gianni , Neviani Erasmo , Lazzi Camilla
Published: January 2019

Background: Lactic acid bacteria (LAB) exhibit a great biodiversity that can be exploited for different purposes, such as to enhance flavours or metabolize phenolic compounds. In the present study, the use of dairy and plant-derived LAB strains to perform cherry juice fermentation is reported. Methods: The growth ability of Lactobacillus plantarum, Lactobacillus casei, Lactobacillus paracasei and Lactobacillus rhamnosus was studied in cherry juice. Profiling of sugars, organic acids and volatile compounds was performed by GC-MS (Gas Chromatography-Mass Spectrometry), while the phenolic fraction was characterized using UHPLC (Ultra High Performance Liquid Chromatography) equipped with a linear ion trap-mass spectrometer. Results: Sucrose significantly decreased in all fermented samples as well as malic acid, converted to lactic acid by malolactic fermentation. The total amount of volatile compounds increased. Specifically, propyl acetate, an ester with fruit notes, reached the highest concentration in L. rhamnosus and L. paracasei (dairy strains) fermented juices. Phenolics were extensively metabolized: caffeic acid was converted into dihydrocaffeic acid, p-coumaric acid into 4-ethylphenol and phenyllactic acid was produced. Conclusion: Lactic acid fermentation confer fruit notes to the juice and enhance phenyllactic acids, especially employing dairy strains (L. rhamnosus and L. paracasei). The level of dihydrocaffeic acid, a compound with putative biological activity was also increased (in particular with L. plantarum).
Toll-Like Receptor-Dependent Immunomodulatory Activity of Pycnogenol®
Authors: Verlaet Annelies , van der Bolt Nieke , Meijer Ben , Breynaert Annelies , Naessens Tania , Konstanti Prokopis , Smidt Hauke , Hermans Nina , Savelkoul Huub F.J. , Teodorowicz Malgorzata
Published: January 2019

Background: Pycnogenol® (PYC), an extract of French maritime pine bark, is widely used as a dietary supplement. PYC has been shown to exert anti-inflammatory actions via inhibiting the Toll-like receptor 4 (TLR4) pathway. However, the role of the other receptors from the TLR family in the immunomodulatory activity of PYC has not been described so far. Aim: The aim of this study was to investigate whether PYC might exert its immunomodulatory properties through cell membrane TLRs (TLR1/2, TLR5, and TLR2/6) other than TLR4. Moreover, the effect of gastrointestinal metabolism on the immunomodulatory effects of PYC was investigated. Findings: We showed that intact non-metabolized PYC dose-dependently acts as an agonist of TLR1/2 and TLR2/6 and as a partial agonist of TLR5. PYC on its own does not agonize or antagonize TLR4. However, after the formation of complexes with lipopolysaccharides (LPS), it is a potent activator of TLR4 signaling. Gastrointestinal metabolism of PYC revealed the immunosuppressive potential of the retentate fraction against TLR1/2 and TLR2/6 when compared to the control fraction containing microbiota and enzymes only. The dialyzed fraction containing PYC metabolites revealed the capacity to induce anti-inflammatory IL-10 secretion. Finally, microbially metabolized PYC affected the colonic microbiota composition during in vitro gastrointestinal digestion. Conclusions: This study showed that gastrointestinal metabolism of PYC reveals its biological activity as a potential inhibitor of TLRs signaling. The results suggest that metabolized PYC acts as a partial agonist of TLR1/2 and TLR2/6 in the presence of the microbiota-derived TLR agonists (retentate fraction) and that it possesses anti-inflammatory potential reflected by the induction of IL-10 from THP-1 macrophages (dialysate fraction).
Are Raw BIA Variables Useful for Predicting Resting Energy Expenditure in Adults with Obesity?
Authors: Marra Maurizio , Cioffi Iolanda , Sammarco Rosa , Santarpia Lidia , Contaldo Franco , Scalfi Luca , Pasanisi Fabrizio
Published: January 2019

This study aimed to develop and validate new predictive equations for resting energy expenditure (REE) in a large sample of subjects with obesity also considering raw variables from bioimpedance-analysis (BIA). A total of 2225 consecutive obese outpatients were recruited and randomly assigned to calibration (n = 1680) and validation (n = 545) groups. Subjects were also split into three subgroups according to their body mass index (BMI). The new predictive equations were generated using two models: Model 1 with age, weight, height, and BMI as predictors, and Model 2 in which raw BIA variables (bioimpedance-index and phase angle) were added. Our results showed that REE was directly correlated with all anthropometric and raw-BIA variables, while the correlation with age was inverse. All the new predictive equations were effective in estimating REE in both sexes and in the different BMI subgroups. Accuracy at the individual level was high for specific group-equation especially in subjects with BMI > 50 kg/m2. Therefore, new equations based on raw-BIA variables were as accurate as those based on anthropometry. Equations developed for BMI categories did not substantially improve REE prediction, except for subjects with a BMI > 50 kg/m2. Further studies are required to verify the application of those formulas and the role of raw-BIA variables for predicting REE.
Soil Zinc Is Associated with Serum Zinc But Not with Linear Growth of Children in Ethiopia
Authors: Tessema Masresha , De Groote Hugo , D. Brouwer Inge , J.M. Feskens Edith , Belachew Tefera , Zerfu Dilnesaw , Belay Adamu , Demelash Yoseph , S. Gunaratna Nilupa
Published: January 2019

To our knowledge, the relationships among soil zinc, serum zinc and children’s linear growth have not been studied geographically or at a national level in any country. We use data from the cross-sectional, nationally representative Ethiopian National Micronutrient Survey (ENMS) (n = 1776), which provided anthropometric and serum zinc (n = 1171) data on children aged 6–59 months. Soil zinc levels were extracted for each child from the digital soil map of Ethiopia, developed by the Africa Soil Information Service. Children’s linear growth was computed using length/height and age converted into Z-scores for height-for-age. Multi-level mixed linear regression models were used for the analysis. Nationally, 28% of children aged 6–59 months were zinc deficient (24% when adjusted for inflammation) and 38% were stunted. Twenty percent of households in the ENMS were located on zinc-deficient soils. Soil zinc (in mg/kg) was positively associated with serum zinc (in µg/dL) (b = 0.9, p = 0.020) and weight-for-height-Z-score (b = 0.05, p = 0.045) but linear growth was not associated with soil zinc (p = 0.604) or serum zinc (p = 0.506) among Ethiopian preschool children. Intervention studies are needed to determine whether there are causal links between soil and human zinc status.
Impact of Malnutrition on Long-Term Mortality in Elderly Patients with Acute Myocardial Infarction
Authors: Komici Klara , Vitale Dino Franco , Mancini Angela , Bencivenga Leonardo , Conte Maddalena , Provenzano Sandra , Grieco Fabrizio Vincenzo , Visaggi Lucia , Ronga Ilaria , Cittadini Antonio , Corbi Graziamaria , Trimarco Bruno , Morisco Carmine , Leosco Dario , Ferrara Nicola , Rengo Giuseppe
Published: January 2019

Background: Malnutrition is a frequent condition in the elderly, and is associated with prolonged hospitalization and increased mortality. However, the impacts of malnutrition among elderly patients with acute myocardial infarction have not been clarified yet. Methods and Results: We enrolled 174 patients aged 65 years and over, admitted with the diagnosis of acute myocardial infarction (AMI), who underwent evaluation of nutritional status by Mini Nutritional Assessment (MNA) and evaluation of mortality risk by GRACE Score 2.0. All-cause mortality was the outcome considered for this study. Over a mean follow-up of 24.5 ± 18.2 months, 43 deaths have been registered (24.3%). Non-survivors were more likely to be older, with worse glomerular filtration rate, lower systolic blood pressure, lower albumin and MNA score, higher prevalence of Killip classification III-IV grade, and higher Troponin I levels. Multivariate Cox proportional analysis revealed that GRACE Score and MNA showed a significant and independent impact on mortality, (HR = 1.76, 95%, CI = 1.34–2.32, and HR = 0.56, 95% CI = 0.42–0.73, respectively). Moreover, the clinical decision curve revealed a higher clinical net benefit when the MNA was included, compared to the partial models without MNA. Conclusion: Nutritional status is an independent predictor of long-term mortality among elderly patients with AMI. MNA score in elderly patients with AMI may help prognostic stratification and identification of patients with, or at risk of, malnutrition in order to apply interventions to improve nutritional status, and maybe survival in this population.