bluuebunny/crossref_metadata_2025 huggingface dataset:
The Combination Projection Method for Solving Convex Feasibility Problems
Authors: He Songnian , Dong Qiao-Li
Published: November 2018

In this paper, we propose a new method, which is called the combination projection method (CPM), for solving the convex feasibility problem (CFP) of finding some x * ∈ C : = ∩ i = 1 m { x ∈ H | c i ( x ) ≤ 0 } , where m is a positive integer, H is a real Hilbert space, and { c i } i = 1 m are convex functions defined as H . The key of the CPM is that, for the current iterate x k , the CPM firstly constructs a new level set H k through a convex combination of some of { c i } i = 1 m in an appropriate way, and then updates the new iterate x k + 1 only by using the projection P H k . We also introduce the combination relaxation projection methods (CRPM) to project onto half-spaces to make CPM easily implementable. The simplicity and easy implementation are two advantages of our methods since only one projection is used in each iteration and the projections are also easy to calculate. The weak convergence theorems are proved and the numerical results show the advantages of our methods.
Changes of Left and Right Ventricle Mechanics and Function in Patients with End-Stage Renal Disease Undergoing Haemodialysis
Authors: Tamulėnaitė Eglė , Žvirblytė Rūta , Ereminienė Rūta , Žiginskienė Edita , Ereminienė Eglė
Published: November 2018

Background and objectives: Chronic kidney disease (CKD) increases the risk of cardiovascular diseases even in its early stages and is associated with structural and functional cardiac abnormalities. The aim of this study was to use speckle-tracking echocardiography (STE) to evaluate left and right ventricle mechanics and function, markers of subclinical dysfunction in patients with end-stage renal disease (ESRD) undergoing haemodialysis. Methods: Patients with ESRD undergoing regular haemodialysis and with preserved left ventricle (LV) ejection fraction (EF) (n = 38) were enrolled in this retrospective study. The control group consisted of 32 age-matched persons with normal kidney function (glomerular filtration rate (GFR) >90 mL/min/1.73 m2 according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)). Conventional 2D echocardiography and STE were performed in all patients. Results: 70 individuals, 31 (44.29%) males and 39 (55.71%) females, were included in the study. There were no significant differences in age, sex and body surface area between the groups. LV end diastolic diameter did not differ between the groups, while LV myocardial mass index was higher in the group of patients on haemodialysis (111.64 ± 27.99 versus 84.21 ± 16.99, p < 0.001) and LV diastolic dysfunction (LVDD) was found in 31 (81.6%) patients of this group. LV global longitudinal strain (GLS) (−22.43 ± 2.71 versus −24.73 ± 2.03, p < 0.001) and LV global circumferential strain (GCS) at the mitral valve and papillary muscles levels (−18.73 ± 3.49 versus −21.67 ± 2.22, p < 0.001; −18.64 ± 2.75 versus −20.42 ± 2.38, p = 0.005, respectively) were significantly lower in haemodialysis group patients. The parameters of the right ventricle (RV) free wall longitudinal function including RV GLS (−22.63 ± 3.04 versus −25.45 ± 2.48, p < 0.001), were reduced in haemodialysis patients compared with the controls. However, RV fractional area change (FAC) did not differ between the groups (p = 0.19). Conclusion: Patients with ESRD and preserved LV ejection fraction undergoing haemodialysis had a higher prevalence of LVDD and impaired LV longitudinal and circumferential deformation indices, as well as reduced RV longitudinal function and deformation parameters compared with the age-matched healthy controls. STE helps to detect subclinical LV and RV dysfunction in chronic haemodialysis patients.
Reversal of Multidrug Resistance in Human Colon Cancer and Human Leukemia Cells by Three Plant Extracts and Their Major Secondary Metabolites
Authors: Zhou Jun-Xian , Wink Michael
Published: November 2018

Background: We studied the effect of three plant extracts (Glycyrrhiza glabra, Paeonia lactiflora, Eriobotrya japonica) and six of their major secondary metabolites (glycyrrhizic acid, 18β glycyrrhetinic acid, liquiritigenin, isoliquiritigenin, paeoniflorin, ursolic acid) on the multidrug resistant human colon cancer cell line Caco-2 and human leukemia cell line CEM/ADR 5000 as compared to the corresponding sensitive cell line CCRF-CEM, and human colon cancer cells HCT-116, which do not over-express ATP-binding cassette (ABC) transporters. Methods: The cytotoxicity of single substances in sensitive and resistant cells was investigated by MTT assay. We also applied combinations of extracts or single compounds with the chemotherapeutic agent doxorubicin or doxorubicin plus the saponin digitonin. The intracellular retention of the ABC transporter substrates rhodamine 123 and calcein was examined by flow cytometry to explore the effect of the substances on the activity of ABC transporters P-glycoprotein and MRP1. Real-time PCR was applied to analyse the gene expression changes of ABCB1, ABCC1, caspase 3, caspase 8, AhR, CYP1A1, and GSTP1 in resistant cells under the treatment of the substances. Results: All the substances moderately inhibited cell growth in sensitive and resistant cells to some degree. Whereas ursolic acid showed IC50 of 14 and 22 µM in CEM/ADR 5000 and Caco-2 cells, respectively, glycyrrhizic acid and paeoniflorin were inactive with IC50 values above 400 μM. Except for liquiritigenin and isoliquiritigenin, all the other substances reversed MDR in CEM/ADR 5000 and Caco-2 cells to doxorubicin. Ue, ga, 18ga, and urs were powerful reversal agents. In CEM/ADR 5000 cells, high concentrations of all the substances, except Paeonia lactiflora extract, increased calcein or rhodamine 123 retention in a dose-dependent manner. In Caco-2 cells, all the substances, except liquiritigenin, retained rhodamine 123 in a dose-dependent manner. We also examined the effect of the plant secondary metabolite (PSM) panel on the expression of ABCB1, ABCC1, caspase 3, caspase 8, AhR, CYP1A1, and GSTP1 genes in MDR cells. Conclusions: The extracts and individual PSM could reverse MDR in CEM/ADR 5000 and Caco-2 cells, which overexpress ABC transporters, in two- and three-drug combinations. Most of the PSM also inhibited the activity of ABC transporters to some degree, albeit at high concentrations. Ue, ga, 18ga, and urs were identified as potential multidrug resistance (MDR) modulator candidates, which need to be characterized and validated in further studies.
Residual Stress, Mechanical Properties, and Grain Morphology of Ti-6Al-4V Alloy Produced by Ultrasonic Impact Treatment Assisted Wire and Arc Additive Manufacturing
Authors: Yang Yichong , Jin Xin , Liu Changmeng , Xiao Muzheng , Lu Jiping , Fan Hongli , Ma Shuyuan
Published: November 2018

Ultrasonic Impact Treatment (UIT) is an effective technique for surface refinement and residual stress reduction, which is widely used in welding. This study investigates UIT-assisted Wire and Arc Additive manufacturing (WAAM). The residual stress, grain morphology and mechanical properties of post-UIT and as-deposited samples are studied. The result demonstrates that the UIT has a significant influence on the decrease of the residual stress. Moreover, the residual stress of the post-UIT samples is much lower than that of the as-deposited samples. The samples fabricated by UIT-assisted WAAM have a novel, bamboo-like distribution of prior-β grains, an alternating distribution of short columnar grains and equiaxed grains. The grain size of this bamboo-like structure is much smaller than the coarsen columnar grains. In addition, the mechanical properties of the post-UIT and as-deposited samples are compared. The results indicate that the average tensile strength of the post-UIT samples is higher, while the average elongation of the post-UIT samples is lower.
Microfluidic Analyzer Enabling Quantitative Measurements of Specific Intracellular Proteins at the Single-Cell Level
Authors: Liu Lixing , Fan Beiyuan , Wang Diancan , Li Xiufeng , Song Yeqing , Zhang Ting , Chen Deyong , Wang Yixiang , Wang Junbo , Chen Jian
Published: November 2018

This paper presents a microfluidic instrument capable of quantifying single-cell specific intracellular proteins, which are composed of three functioning modules and two software platforms. Under the control of a LabVIEW platform, a pressure module flushed cells stained with fluorescent antibodies through a microfluidic module with fluorescent intensities quantified by a fluorescent module and translated into the numbers of specific intracellular proteins at the single-cell level using a MATLAB platform. Detection ranges and resolutions of the analyzer were characterized as 896.78–6.78 × 105 and 334.60 nM for Alexa 488, 314.60–2.11 × 105 and 153.98 nM for FITC, and 77.03–5.24 × 104 and 37.17 nM for FITC-labelled anti-beta-actin antibodies. As a demonstration, the numbers of single-cell beta-actins of two paired oral tumor cell types and two oral patient samples were quantified as: 1.12 ± 0.77 × 106/cell (salivary adenoid cystic carcinoma parental cell line (SACC-83), ncell = 13,689) vs. 0.90 ± 0.58 × 105/cell (salivary adenoid cystic carcinoma lung metastasis cell line (SACC-LM), ncell = 15,341); 0.89 ± 0.69 × 106/cell (oral carcinoma cell line (CAL 27), ncell = 7357) vs. 0.93 ± 0.69 × 106/cell (oral carcinoma lymphatic metastasis cell line (CAL 27-LN2), ncell = 6276); and 0.86 ± 0.52 × 106/cell (patient I) vs. 0.85 ± 0.58 × 106/cell (patient II). These results (1) validated the developed analyzer with a throughput of 10 cells/s and a processing capability of ~10,000 cells for each cell type, and (2) revealed that as an internal control in cell analysis, the expressions of beta-actins remained stable in oral tumors with different malignant levels.
Role of SCFAs for Fimbrillin-Dependent Biofilm Formation of Actinomyces oris
Authors: Suzuki Itaru , Shimizu Takehiko , Senpuku Hidenobu
Published: November 2018

Actinomyces oris expresses type 1 and 2 fimbriae on the cell surface. Type 2 fimbriae mediate co-aggregation and biofilm formation and are composed of the shaft fimbrillin FimA and the tip fimbrillin FimB. Short-chain fatty acids (SCFAs) are metabolic products of oral bacteria, but the effects of exogenous SCFAs on FimA-dependent biofilm formation are poorly understood. We performed two types of biofilm formation assays using A. oris MG1 or MG1.ΔfimA to observe the effects of SCFAs on FimA-dependent biofilm formation in 96-well and six-well microtiter plates and a flow cell system. SCFAs did not induce six- and 16-hour biofilm formation of A. oris MG1 and MG1.ΔfimA in saliva-coated 96-well and six-well microtiter plates in which metabolites produced during growth were not excluded. However, 6.25 mM butyric acid and 3.125 mM propionic acid induced FimA-dependent biofilm formation and cell death in a flow cell system in which metabolites produced during growth were excluded. Metabolites produced during growth may lead to disturbing effects of SCFAs on the biofilm formation. The pure effects of SCFAs on biofilm formation were induction of FimA-dependent biofilm formation, but the stress responses from dead cells may regulate its effects. Therefore, SCFA may play a key role in A. oris biofilm formation.
Microwave-Assisted Expeditious Synthesis of 2-Alkyl-2-(N-arylsulfonylindol-3-yl)-3-N-acyl-5-aryl-1,3,4-oxadiazolines Catalyzed by HgCl2 under Solvent-Free Conditions as Potential Anti-HIV-1 Agents
Authors: Che Zhiping , Tian Yuee , Liu Shengming , Jiang Jia , Hu Mei , Chen Genqiang
Published: November 2018

A series of 2-alkyl-2-(N-arylsulfonylindol-3-yl)-3-N-acyl-5-aryl-1,3,4-oxadiazolines were expeditious prepared under microwave-assisted, catalyzed by HgCl2 and solvent-free conditions. This method has the advantage of low catalyst loading and recovering catalyst, ease reaction and repaid reaction times, easy separation products and excellent yields, and more conducive to the large-scale synthesis products. Furthermore, compounds 3s, 3y, 3a′, 3b′, 3f′, 3i′, 3q′, and 3r′ exhibited more potent anti-HIV-1 activity with EC50 values of 3.35, 6.12, 3.63, 9.54, 1.79, 0.51, 3.00, and 4.01 μg/mL, and TI values of 32.66, >32.68, 31.22, 13.94, 24.27, 39.59, 26.01, and 24.51, respectively. Especially compound 3i′ displayed the highest anti-HIV-1 activity with TI values of 39.59.
Pretreatment of Lignocellulosic Materials as Substrates for Fermentation Processes
Authors: Kucharska Karolina , Rybarczyk Piotr , Hołowacz Iwona , Łukajtis Rafał , Glinka Marta , Kamiński Marian
Published: November 2018

Lignocellulosic biomass is an abundant and renewable resource that potentially contains large amounts of energy. It is an interesting alternative for fossil fuels, allowing the production of biofuels and other organic compounds. In this paper, a review devoted to the processing of lignocellulosic materials as substrates for fermentation processes is presented. The review focuses on physical, chemical, physicochemical, enzymatic, and microbiologic methods of biomass pretreatment. In addition to the evaluation of the mentioned methods, the aim of the paper is to understand the possibilities of the biomass pretreatment and their influence on the efficiency of biofuels and organic compounds production. The effects of different pretreatment methods on the lignocellulosic biomass structure are described along with a discussion of the benefits and drawbacks of each method, including the potential generation of inhibitory compounds for enzymatic hydrolysis, the effect on cellulose digestibility, the generation of compounds that are toxic for the environment, and energy and economic demand. The results of the investigations imply that only the stepwise pretreatment procedure may ensure effective fermentation of the lignocellulosic biomass. Pretreatment step is still a challenge for obtaining cost-effective and competitive technology for large-scale conversion of lignocellulosic biomass into fermentable sugars with low inhibitory concentration.
Enhanced Stability of DNA Oligonucleotides with Partially Zwitterionic Backbone Structures in Biological Media
Authors: Meng Melissa , Schmidtgall Boris , Ducho Christian
Published: November 2018

Deficient stability towards nuclease-mediated degradation is one of the most relevant tasks in the development of oligonucleotide-derived biomedical agents. This hurdle can be overcome through modifications to the native oligonucleotide backbone structure, with the goal of simultaneously retaining the unique hybridization properties of nucleic acids. The nucleosyl amino acid (NAA)-modification is a recently introduced artificial cationic backbone linkage. Partially zwitterionic NAA-modified oligonucleotides had previously shown hybridization with DNA strands with retained base-pairing fidelity. In this study, we report the significantly enhanced stability of NAA-modified oligonucleotides towards 3′- and 5′-exonuclease-mediated degradation as well as in complex biological media such as human plasma and whole cell lysate. This demonstrates the potential versatility of the NAA-motif as a backbone modification for the development of biomedically active oligonucleotide analogues.
Leptodactylus latrans Amphibian Skin Secretions as a Novel Source for the Isolation of Antibacterial Peptides
Authors: Siano Alvaro , Humpola Maria Veronica , De Oliveira Eliandre , Albericio Fernando , Simonetta Arturo C. , Lajmanovich Rafael , Tonarelli Georgina G.
Published: November 2018

Amphibians´ skin produces a diverse array of antimicrobial peptides that play a crucial role as the first line of defense against microbial invasion. Despite the immense richness of wild amphibians in Argentina, current knowledge about the presence of peptides with antimicrobial properties is limited to a only few species. Here we used LC-MS-MS to identify antimicrobial peptides with masses ranging from 1000 to 4000 Da from samples of skin secretions of Leptodactylus latrans (Anura: Leptodactylidae). Three novel amino acid sequences were selected for chemical synthesis and further studies. The three synthetic peptides, named P1-Ll-1577, P2-Ll-1298, and P3-Ll-2085, inhibited the growth of two ATCC strains, namely Escherichia coli and Staphylococcus aureus. P3-Ll-2085 was the most active peptide. In the presence of trifluoroethanol (TFE) and anionic liposomes, it adopted an amphipathic α-helical structure. P2-Ll-1298 showed slightly lower activity than P3-Ll-2085. Comparison of the MIC values of these two peptides revealed that the addition of seven amino acid residues (GLLDFLK) on the N-terminal of P2-Ll-1298 significantly improved activity against both strains. P1-Ll-1577, which remarkably is an anionic peptide, showed interesting antimicrobial activity against E. coli and S. aureus strain, showing marked membrane selectivity and non-hemolysis. Due to this, P1-L1-1577 emerges as a potential candidate for the development of new antibacterial drugs.
An Intelligent Nanoscale Insulin Delivery System
Authors: Wang Wei , Liao Ling , Zhang Xiaobing , Lei Fan , Zhang Yaou , Liu Gan , Xie Weidong
Published: November 2018

Insulin injection relies on strict blood glucose monitoring. However, existing techniques and algorithms for blood glucose monitoring cannot be completed in a timely way. In this study, we have developed a new intelligent glucose-sensitive insulin delivery system to stabilize blood glucose levels in the body. This system does not require real-time detection of blood glucose. First, we successfully synthesized a nanoscale material called PAM-PAspPBA-b-PEG by using chemical methods. We then conducted TEM, DLS, and 1H-NMR analyses to characterize the physicochemical properties, such as size, molecular composition, and configuration of the nanomaterial. We verified the glucose responsibility of the insulin loading nanoscale material in vitro and evaluated its safety and effect on mice in vivo. Results showed that insulin-loaded PAM-PAspPBA-b-PEG is glucose-sensitive, safer and more effective than regular insulin injection. This study provides a basis for future development of smart insulin delivery systems.
Metal Organic Frameworks Based Materials for Heterogeneous Photocatalysis
Authors: Zhao Shu-Na , Wang Guangbo , Poelman Dirk , Van Der Voort Pascal
Published: November 2018

The increase in environmental pollution due to the excessive use of fossil fuels has prompted the development of alternative and sustainable energy sources. As an abundant and sustainable energy, solar energy represents the most attractive and promising clean energy source for replacing fossil fuels. Metal organic frameworks (MOFs) are easily constructed and can be tailored towards favorable photocatalytic properties in pollution degradation, organic transformations, CO2 reduction and water splitting. In this review, we first summarize the different roles of MOF materials in the photoredox chemical systems. Then, the typical applications of MOF materials in heterogeneous photocatalysis are discussed in detail. Finally, the challenges and opportunities in this promising field are evaluated.
From Quinoxaline, Pyrido[2,3-b]pyrazine and Pyrido[3,4-b]pyrazine to Pyrazino-Fused Carbazoles and Carbolines
Authors: Lassagne Frédéric , Langlais Timothy , Caytan Elsa , Limanton Emmanuelle , Paquin Ludovic , Boullard Manon , Courtel Coline , Curbet Idriss , Gédéon Clément , Lebreton Julien , Picot Laurent , Thiéry Valérie , Souab Mohamed , Baratte Blandine , Ruchaud Sandrine , Bach Stéphane , Roisnel Thierry , Mongin Florence
Published: November 2018

2,3-Diphenylated quinoxaline, pyrido[2,3-b]pyrazine and 8-bromopyrido[3,4-b]pyrazine were halogenated in deprotometalation-trapping reactions using mixed 2,2,6,6-tetramethyl piperidino-based lithium-zinc combinations in tetrahydrofuran. The 2,3-diphenylated 5-iodo- quinoxaline, 8-iodopyrido[2,3-b]pyrazine and 8-bromo-7-iodopyrido[3,4-b]pyrazine thus obtained were subjected to palladium-catalyzed couplings with arylboronic acids or anilines, and possible subsequent cyclizations to afford the corresponding pyrazino[2,3-a]carbazole, pyrazino[2′,3′:5,6] pyrido[4,3-b]indole and pyrazino[2′,3′:4,5]pyrido[2,3-d]indole, respectively. 8-Iodopyrido[2,3-b] pyrazine was subjected either to a copper-catalyzed C-N bond formation with azoles, or to direct substitution to introduce alkylamino, benzylamino, hydrazine and aryloxy groups at the 8 position. The 8-hydrazino product was converted into aryl hydrazones. Most of the compounds were evaluated for their biological properties (antiproliferative activity in A2058 melanoma cells and disease-relevant kinase inhibition).
Next Generation Sequencing-Based Molecular Marker Development: A Case Study in Betula Alnoides
Authors: Tan Jing , Guo Jun-Jie , Yin Ming-Yu , Wang Huan , Dong Wen-Pan , Zeng Jie , Zhou Shi-Liang
Published: November 2018

Betula alnoides is a fast-growing valuable indigenous tree species with multiple uses in the tropical and warm subtropical regions in South-East Asia and southern China. It has been proved to be tetraploid in most parts of its distribution in China. In the present study, next generation sequencing (NGS) technology was applied to develop numerous SSR markers for B. alnoides, and 64,376 contig sequences of 106,452 clean reads containing 164,357 candidate SSR loci were obtained. Among the derived SSR repeats, mono-nucleotide was the main type (77.05%), followed by di- (10.18%), tetra- (6.12%), tri- (3.56%), penta- (2.14%) and hexa-nucleotide (0.95%). The short nucleotide sequence repeats accounted for 90.79%. Among the 291 repeat motifs, AG/CT (46.33%) and AT/AT (44.15%) were the most common di-nucleotide repeats, while AAT/ATT (48.98%) was the most common tri-nucleotide repeats. A total of 2549 primer sets were designed from the identified putative SSR regions of which 900 were randomly selected for evaluation of amplification successfulness and detection of polymorphism if amplified successfully. Three hundred and ten polymorphic markers were obtained through testing with 24 individuals from B. alnoides natural forest in Jingxi County, Guangxi, China. The number of alleles (NA) of each marker ranged from 2 to 19 with a mean of 5.14. The observed (HO) and expected (HE) heterozygosities varied from 0.04 to 1.00 and 0.04 to 0.92 with their means being 0.64 and 0.57, respectively. Shannon-Wiener diversity index (I) ranged from 0.10 to 2.68 with a mean of 1.12. Cross-species transferability was further examined for 96 pairs of SSR primers randomly selected, and it was found that 48.96–84.38% of the primer pairs could successfully amplify each of six related Betula species. The obtained SSR markers can be used to study population genetics and molecular marker assisted breeding, particularly genome-wide association study of these species in the future.
Stereogenic Centers
Authors: Baeza Alejandro
Published: November 2018

The demand for chiral organic entities for different industrial purposes has grown exponentially in the last decades. [...]
The Development of Assays for Heparanase Enzymatic Activity: Towards a Gold Standard
Authors: Chhabra Mohit , Ferro Vito
Published: November 2018

The enzyme heparanase, an endo-β-glucuronidase, degrades heparan sulfate (HS) chains on the cell surface and in the extracellular matrix. Heparanase regulates numerous biological processes that drive tumour growth, metastasis and angiogenesis. In addition to its key role in cancer progression, it has also been implicated in an ever-growing number of other diseases, particularly those associated with inflammation. The importance of heparanase in biology has led to numerous efforts over the years to develop assays to monitor its activity and to screen for new inhibitors as potential drug candidates. Despite these efforts and the commercialization of a few kits, most heparanase assays are still complex, labour intensive, costly or have limited application. Herein we review the various methods for assaying heparanase enzymatic activity, focusing on recent developments towards new assays that hold the promise of accelerating research into this important enzyme.
Two-Dimensional Fluorescence Lifetime Correlation Spectroscopy: Concepts and Applications
Authors: Otosu Takuhiro , Yamaguchi Shoichi
Published: November 2018

We review the basic concepts and recent applications of two-dimensional fluorescence lifetime correlation spectroscopy (2D FLCS), which is the extension of fluorescence correlation spectroscopy (FCS) to analyze the correlation of fluorescence lifetime in addition to fluorescence intensity. Fluorescence lifetime is sensitive to the microenvironment and can be a “molecular ruler” when combined with FRET. Utilization of fluorescence lifetime in 2D FLCS thus enables us to quantify the inhomogeneity of the system and the interconversion dynamics among different species with a higher time resolution than other single-molecule techniques. Recent applications of 2D FLCS to various biological systems demonstrate that 2D FLCS is a unique and promising tool to quantitatively analyze the microsecond conformational dynamics of macromolecules at the single-molecule level.
Antitumor Effect of the Essential Oil from the Leaves of Croton matourensis Aubl. (Euphorbiaceae)
Authors: Lima Emilly J. S. P. de , Alves Rafaela G. , D´Elia Gigliola M. A. , Anunciação Talita A. da , Silva Valdenizia R. , Santos Luciano de S. , Soares Milena B. P. , Cardozo Nállarett M. D. , Costa Emmanoel V. , Silva Felipe M. A. da , Koolen Hector H. F. , Bezerra Daniel P.
Published: November 2018

Croton matourensis Aubl. (synonym Croton lanjouwensis Jabl.), popularly known as “orelha de burro”, “maravuvuia”, and/or “sangrad’água”, is a medicinal plant used in Brazilian folk medicine as a depurative and in the treatment of infections, fractures, and colds. In this work, we investigated the chemical composition and in vitro cytotoxic and in vivo antitumor effects of the essential oil (EO) from the leaves of C. matourensis collected from the Amazon rainforest. The EO was obtained by hydrodistillation using a Clevenger-type apparatus and characterized qualitatively and quantitatively by gas chromatography coupled to mass spectrometry (GC–MS) and gas chromatography with flame ionization detection (GC–FID), respectively. In vitro cytotoxicity of the EO was assessed in cancer cell lines (MCF-7, HCT116, HepG2, and HL-60) and the non-cancer cell line (MRC-5) using the Alamar blue assay. Furthermore, annexin V-FITC/PI staining and the cell cycle distribution were evaluated with EO-treated HepG2 cells by flow cytometry. In vivo efficacy of the EO (40 and 80 mg/kg/day) was demonstrated in C.B-17 severe combined immunodeficient (SCID) mice with HepG2 cell xenografts. The EO included β-caryophyllene, thunbergol, cembrene, p-cymene, and β-elemene as major constituents. The EO exhibited promising cytotoxicity and was able to cause phosphatidylserine externalization and DNA fragmentation without loss of the cell membrane integrity in HepG2 cells. In vivo tumor mass inhibition rates of the EO were 34.6% to 55.9%. Altogether, these data indicate the anticancer potential effect of C. matourensis.
Immobilized Gold Nanoparticles Prepared from Gold(III)-Containing Ionic Liquids on Silica: Application to the Sustainable Synthesis of Propargylamines
Authors: Soengas Raquel , Navarro Yolanda , Iglesias María José , López-Ortiz Fernando
Published: November 2018

A cycloaurated phosphinothioic amide gold(III) complex was supported on amorphous silica with the aid of an imidazolium ionic liquid (IL) physisorbed in the SiO2 pores (SiO2–IL) and covalently bonded to the SiO2 (SiO2@IL). Gold(0) nanoparticles (AuNPs) were formed in situ and subsequently immobilized on the SiO2–IL/SiO2@IL phase. The resulting catalytic systems Au–SiO2–IL and Au–SiO2@IL promoted the solvent-free A3 coupling reaction of alkynes, aldehydes, and amines in high yields under solvent-free conditions with very low catalyst loading and without the use of additives. The Au–SiO2@IL catalyst showed good recyclability and could be reused at least five times with yields of propargylamines of ≥80%. This synthetic method provides a green and low cost way to effectively prepare propargylamines. Additionally, 31P high resolution magic angle spinning (HRMAS) NMR spectroscopy is introduced as a simple technique to establish the Au loading of the catalyst.
Biological Activity of the Carrier as a Factor in Immunogen Design for Haptens
Authors: Ertekin Özlem , Akçael Esin , Kocaağa Harun , Öztürk Selma
Published: November 2018

Immunoanalytical methods are frequently employed in the detection of hazardous small molecular weight compounds. However, antibody development for these molecules is a challenge, because they are haptens and cannot induce a humoral immune response in experimental animals. Immunogenic forms of haptens are usually prepared by conjugating them to a protein carrier which serves as an immune stimulator. However, the carrier is usually considered merely as a bulk mass, and its biological activity is ignored. Here, we induced an endocytic receptor, transferrin receptor, by selecting its ligand as a carrier protein to enhance antibody production. We conjugated aflatoxin, a potent carcinogenic food contaminant, to transferrin and evaluated its potential to stimulate antibody production with respect to ovalbumin conjugates. Transferrin conjugates induced aflatoxin-specific immune responses in the second immunization, while ovalbumin conjugates reached similar antibody titers after 5 injections. Monoclonal antibodies were successfully developed with mice immunized with either of the conjugates.
Comparison of Low Glycaemic Index and High Glycaemic Index Potatoes in Relation to Satiety: A Single-Blinded, Randomised Crossover Study in Humans
Authors: Andersen Sabina S. H. , Heller Jonas M. F. , Hansen Thea Toft , Raben Anne
Published: November 2018

High glycaemic index (GI) foods have been proposed to reduce satiety and thus promote overweight and obesity. Generally, potatoes have a high GI, but they also provide many beneficial nutrients and they are a highly important food source globally. In this study, we investigated how a low GI potato affected subjective satiety as compared to a high GI potato. Twenty healthy men (aged 18–40 years; body mass index (BMI) 18–27 kg/m2) participated in this single-blinded, controlled, randomised crossover trial. On each of the two trial days, the subjects were given a 500-gram portion of either a low or high GI potato variety (Carisma® low GI and Arizona high GI). Subjective appetite sensations were measured at baseline and at +15 min, +45 min, +75 min, +105 min, and +135 min after consumption of the test meal until an ad libitum meal was served at +150 min. No significant differences in the primary endpoint, satiety, were found between the two potato varieties (all p > 0.05). Furthermore, no significant differences were found in the secondary endpoints; hunger, fullness, and prospective food consumption, or ad libitum energy intake (all p > 0.05). In conclusion, the results of this study do not indicate that the GI of potatoes is important for satiety in normal-weight men.
Nutrient Supplement Use among the Chinese Population: A Cross-Sectional Study of the 2010–2012 China Nutrition and Health Surveillance
Authors: Gong Weiyan , Liu Ailing , Yao Yecheng , Ma Yanning , Ding Caicui , Song Chao , Yuan Fan , Zhang Yan , Feng Ganyu , Chen Zheng , Ding Gangqiang
Published: November 2018

Nutrient supplements play a key role in managing malnutrition/chronic diseases and are commonly used in the world, but few studies described the prevalence of nutrient supplement use at the national level in China. To our knowledge, this study provides the first detailed investigation of nutrient supplement use in a nationally representative sample of the Chinese population. This study aimed to describe the prevalence of the nutrient supplement use among the Chinese population aged 6 years or older in 2010–2012. A stratified multistage cluster sampling method was conducted to recruit participants from 150 surveillance sites. The demographic characteristics and information about nutrient supplement use were collected through an interview-administrative questionnaire. A total of 74,501 children and adults (excluding the pregnant women) were included in the study (mean age, 35.7 years; male, 47.0%, female, 53.5%). Only 0.71% of the participants reported using nutrient supplements in the previous month. Participants aged 6–11 years and 60 years and above, female, living in large urban, with higher education level and higher family incomes were more likely to use nutrient supplements than their counterparts (p < 0.05). The prevalence of nutrient supplement use increased with age in Chinese adults. The highest usage among the nutrient supplements was multi-vitamins and minerals with 0.37%. More females used single vitamin, multi-mineral, multi-vitamins and minerals than males (p < 0.05). The nutrient supplement use proportion was highest amongst the participants with a health problem, and the participants who had no idea about their health conditions were the least likely to use the nutrient supplements (p < 0.05). The prevalence of nutrient supplement use was low among the Chinese population in 2010–2012. Further research is required to understand the social cognition, usage reasons, dosage and consumption motivation of NS, and the relationships with health effects, to ensure that the nutrient supplements can be appropriately promoted in China.
Dietary Flavonoid Intakes Are Associated with Race but Not Income in an Urban Population
Authors: Fanelli Kuczmarski Marie , Sebastian Rhonda S. , Goldman Joseph D. , Murayi Theophile , Steinfeldt Lois C. , Eosso Jessica R. , Moshfegh Alanna J. , Zonderman Alan B. , Evans Michele K.
Published: November 2018

Flavonoids are polyphenolic phytochemicals with health-promoting properties, yet knowledge about their intake in at-risk populations is limited. This study sought to estimate intakes of total flavonoids and six flavonoid classes in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study; determine if differences in intakes exist by race (African American (AA) and White (W)) and income (< or >125% Federal poverty guidelines); and compare intakes to those of a nationally representative population with similar demographic and socioeconomic characteristics. Data transformation normalized the flavonoid intake distributions prior to conducting statistical tests. With the exception of the flavanone class, flavonoid intakes of AAs were significantly lower than those of W (p < 0.01), regardless of other potential mediating factors including sex, age, and income. Total flavonoid intakes in HANDLS did not differ from intakes in the nationally representative study, but anthocyanidin and flavone intakes were lower, and race specific differences were found for several flavonoid classes. These findings imply that benefits attributable to flavonoid consumption may not be experienced equally by AAs and Whites, nor in vulnerable populations such as that represented by HANDLS relative to the U.S. population, and may play a role in observed health disparities.
Response to “Are There Non-Responders to the Ergogenic 3 Effects of Caffeine Ingestion on Exercise Performance?”
Authors: Southward Kyle , Rutherfurd-Markwick Kay , Badenhorst Claire , Ali Ajmol
Published: November 2018

In response to “Letter: are there non-responders to the ergogenic effects of caffeine ingestion on exercise performance” by Grgic [...]
Hydrocortisone, Ascorbic Acid and Thiamine (HAT Therapy) for the Treatment of Sepsis. Focus on Ascorbic Acid
Authors: Marik Paul E.
Published: November 2018

Sepsis is a devastating disease that carries an enormous toll in terms of human suffering and lives lost. Over 100 novel pharmacologic agents that targeted specific molecules or pathways have failed to improve the outcome of sepsis. Preliminary data suggests that the combination of Hydrocortisone, Ascorbic Acid and Thiamine (HAT therapy) may reduce organ failure and mortality in patients with sepsis and septic shock. HAT therapy is based on the concept that a combination of readily available, safe and cheap agents, which target multiple components of the host’s response to an infectious agent, will synergistically restore the dysregulated immune response and thereby prevent organ failure and death. This paper reviews the rationale for HAT therapy with a focus on vitamin C.
Gut Microbiota and Their Neuroinflammatory Implications in Alzheimer’s Disease
Authors: Giau Vo , Wu Si , Jamerlan Angelo , An Seong , Kim SangYun , Hulme John
Published: November 2018

The bidirectional communication between the central nervous system (CNS) and the gut microbiota plays a pivotal role in human health. Increasing numbers of studies suggest that the gut microbiota can influence the brain and behavior of patients. Various metabolites secreted by the gut microbiota can affect the cognitive ability of patients diagnosed with neurodegenerative diseases. Nearly one in every ten Korean senior citizens suffers from Alzheimer’s disease (AD), the most common form of dementia. This review highlights the impact of metabolites from the gut microbiota on communication pathways between the brain and gut, as well as the neuroinflammatory roles they may have in AD patients. The objectives of this review are as follows: (1) to examine the role of the intestinal microbiota in homeostatic communication between the gut microbiota and the brain, termed the microbiota–gut–brain (MGB) axis; (2) to determine the underlying mechanisms of signal dysfunction; and (3) to assess the impact of signal dysfunction induced by the microbiota on AD. This review will aid in understanding the microbiota of elderly people and the neuroinflammatory roles they may have in AD.
TNBC Challenge: Oligonucleotide Aptamers for New Imaging and Therapy Modalities
Authors: Camorani Simona , Fedele Monica , Zannetti Antonella , Cerchia Laura
Published: November 2018

Compared to other breast cancers, triple-negative breast cancer (TNBC) usually affects younger patients, is larger in size, of higher grade and is biologically more aggressive. To date, conventional cytotoxic chemotherapy remains the only available treatment for TNBC because it lacks expression of the estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2), and no alternative targetable molecules have been identified so far. The high biological and clinical heterogeneity adds a further challenge to TNBC management and requires the identification of new biomarkers to improve detection by imaging, thus allowing the specific treatment of each individual TNBC subtype. The Systematic Evolution of Ligands by EXponential enrichment (SELEX) technique holds great promise to the search for novel targetable biomarkers, and aptamer-based molecular approaches have the potential to overcome obstacles of current imaging and therapy modalities. In this review, we highlight recent advances in oligonucleotide aptamers used as imaging and/or therapeutic agents in TNBC, discussing the potential options to discover, image and hit new actionable targets in TNBC.
Polyamidoamine Nanoparticles for the Oral Administration of Antimalarial Drugs
Authors: Martí Coma-Cros Elisabet , Biosca Arnau , Marques Joana , Carol Laura , Urbán Patricia , Berenguer Diana , Riera Maria Cristina , Delves Michael , Sinden Robert E. , Valle-Delgado Juan José , Spanos Lefteris , Siden-Kiamos Inga , Pérez Paula , Paaijmans Krijn , Rottmann Matthias , Manfredi Amedea , Ferruti Paolo , Ranucci Elisabetta , Fernàndez-Busquets Xavier
Published: November 2018

Current strategies for the mass administration of antimalarial drugs demand oral formulations to target the asexual Plasmodium stages in the peripheral bloodstream, whereas recommendations for future interventions stress the importance of also targeting the transmission stages of the parasite as it passes between humans and mosquitoes. Orally administered polyamidoamine (PAA) nanoparticles conjugated to chloroquine reached the blood circulation and cured Plasmodium yoelii-infected mice, slightly improving the activity of the free drug and inducing in the animals immunity against malaria. Liquid chromatography with tandem mass spectrometry analysis of affinity chromatography-purified PAA ligands suggested a high adhesiveness of PAAs to Plasmodium falciparum proteins, which might be the mechanism responsible for the preferential binding of PAAs to Plasmodium-infected erythrocytes vs. non-infected red blood cells. The weak antimalarial activity of some PAAs was found to operate through inhibition of parasite invasion, whereas the observed polymer intake by macrophages indicated a potential of PAAs for the treatment of certain coinfections such as Plasmodium and Leishmania. When fluorescein-labeled PAAs were fed to females of the malaria mosquito vectors Anopheles atroparvus and Anopheles gambiae, persistent fluorescence was observed in the midgut and in other insect’s tissues. These results present PAAs as a versatile platform for the encapsulation of orally administered antimalarial drugs and for direct administration of antimalarials to mosquitoes, targeting mosquito stages of Plasmodium.
Optimized Chitosan/Anion Polyelectrolyte Complex Based Inserts for Vaginal Delivery of Fluconazole: In Vitro/In Vivo Evaluation
Authors: Darwesh Bayan , Aldawsari Hibah M. , Badr-Eldin Shaimaa M.
Published: November 2018

(1) Background: Fluconazole, used orally for vaginal candidiasis, has reported gastrointestinal side effects. Therefore, researchers directed towards the drug vaginal delivery. However, vaginal delivery is limited by poor retention and leakage. Thus, this work aimed at exploring chitosan/anion polyelectrolyte complex (PEC) for the formulation of fluconazole vaginal inserts with controlled release and appreciable mucoadhesion. (2) Methods: PECs were prepared and assessed for interactions. Fluconazole PEC based vaginal inserts were prepared by lyophilization using mannitol. 3151 factorial design was applied to investigate the effect of the anion type and Chitosan/anion ratio on the inserts mucoadhesion and release properties. The optimized insert [based on 5:5 chitosan: anionic polymer (sodium alginate)] release was modulated by the release retardant; Compritol® 888. The selected formulation was subjected to microbiological and histological evaluation. (3) Results: Fluconazole inserts showed satisfactory drug content, acceptable friability percentages and highest swelling indices at six hours. Statistical analysis showed significant effect of the studied factors on detachment force and release properties. Microbiological assays revealed significantly higher antifungal activity of inserts compared to fluconazole solution. Reduced inflammatory cells were confirmed by histological evaluation. (4) Conclusion: CH/Alg based vaginal insert could be a promising platform for vaginal delivery of antifungal drugs used for vaginal candidiasis treatment.
Solid Lipid Nanoparticles for Dibucaine Sustained Release
Authors: De M. Barbosa Raquel , Ribeiro Ligia N. M. , Casadei Bruna R. , Da Silva Camila M. G. , Queiróz Viviane A. , Duran Nelson , De Araújo Daniele R. , Severino Patrícia , De Paula Eneida
Published: November 2018

Dibucaine (DBC) is among the more potent long-acting local anesthetics (LA), and it is also one of the most toxic. Over the last decades, solid lipid nanoparticles (SLN) have been developed as promising carriers for drug delivery. In this study, SLN formulations were prepared with the aim of prolonging DBC release and reducing its toxicity. To this end, SLN composed of two different lipid matrices and prepared by two different hot-emulsion techniques (high-pressure procedure and sonication) were compared. The colloidal stability of the SLN formulations was tracked in terms of particle size (nm), polydispersity index (PDI), and zeta potential (mV) for 240 days at 4 °C; the DBC encapsulation efficiency was determined by the ultrafiltration/centrifugation method. The formulations were characterized by differential scanning calorimetry (DSC), electron paramagnetic resonance (EPR), and release kinetic experiments. Finally, the in vitro cytotoxicity against 3T3 fibroblast and HaCaT cells was determined, and the in vivo analgesic action was assessed using the tail flick test in rats. Both of the homogenization procedures were found suitable to produce particles in the 200 nm range, with good shelf stability (240 days) and high DBC encapsulation efficiency (~72–89%). DSC results disclosed structural information on the nanoparticles, such as the lower crystallinity of the lipid core vs. the bulk lipid. EPR measurements provided evidence of DBC partitioning in both SLNs. In vitro (cytotoxicity) and in vivo (tail flick) experiments revealed that the encapsulation of DBC into nanoparticles reduces its intrinsic cytotoxicity and prolongs the anesthetic effect, respectively. These results show that the SLNs produced are safe and have great potential to extend the applications of dibucaine by enhancing its bioavailability.
Synthesis and Applications of Molecularly Imprinted Polymers Modified TiO2 Nanomaterials: A Review
Authors: Sun Lingna , Guan Jie , Xu Qin , Yang Xiaoyu , Wang Juan , Hu Xiaoya
Published: November 2018

Titanium dioxide (TiO2) nanomaterials have caused a widespread concern in the past several decades for their bulk characteristics and potential applications in many different areas. Lately, the combination between molecularly imprinted polymers (MIPs) and TiO2 nanomaterials have been proven to improve the relative adsorption capacity, selectivity and accelerate the rate of mass transfer of analyte which is not possible using TiO2 alone. Considering the unique performance of the MIPs modified TiO2 nanomaterials, this review intends to give an overview of the recent progresses in the development of MIPs modified TiO2 nanomaterials, the potential applications of their tailor-made characteristics. The limitations and challenges in this practically promising nanomaterials have also been raised and summarized. By means of the points raised in this article, we would like to provide some assistance for further development of preparation methodologies and the expansion of some potential applications in the field of MIPs modified TiO2 nanomaterials.
The Effect of Substances of Plant Origin on the Thermal and Thermo-Oxidative Ageing of Aliphatic Polyesters (PLA, PHA)
Authors: Masek Anna , Latos-Brozio Malgorzata
Published: November 2018

The stabilization efficiency of flavonoids (rutin and hesperidin) in polyester (polylactide (PLA) and polyhydroxyalkaonate (PHA)) composites under oxygen at high temperature was investigated. The polymer was homogenized with three antioxidants then processed by extrusion. The effects of stabilizers on the following physicochemical properties were investigated: melt flow, Vicat softening temperature, surface energy, and color change (Cie-Lab space). The aim of this study was to improve the stability of aliphatic polyesters by extending and controlling their lifetime. Differential Scanning Calorimetry DSC and Thermogravimetric analysis DTG methods were used to confirm the stabilizing effects (the inhibition of oxidation) of flavonoids (rutin and hesperidin) on the ageing process of biodegradable polymers. The levels of migration of plant antioxidants from PLA and PHA were determined and compared to the industrial stabilizer (Chimassorb 944 UV absorber). Based on this study, a comparable-to-higher efficiency of the proposed flavonoids for the stabilization of polyesters was found when compared to the commercial stabilizers. Thus, in the future, natural plant-derived substances may replace toxic hindered amines, which are commonly used as light stabilizers (HALS—Hindered Amine Light Stabilizers) in the polymer industry.