bluuebunny/crossref_metadata_2025 huggingface dataset:
CLE-10 from Carpesium abrotanoides L. Suppresses the Growth of Human Breast Cancer Cells (MDA-MB-231) In Vitro by Inducing Apoptosis and Pro-Death Autophagy Via the PI3K/Akt/mTOR Signaling Pathway
Authors: Tian Li , Cheng Fan , Wang Lei , Qin Wen , Zou Kun , Chen Jianfeng
Published: March 2019

Background: The antitumor activity of CLE-10 (4-epi-isoinuviscolide), a sesquiterpene lactone compound, isolated from Carpesium abrotanoides L. has rarely been reported. The aim of this study is to investigate the antitumor activity of CLE-10 and give a greater explanation of its underlying mechanisms. Methods: The cytotoxicity of CLE-10 was evaluated using MTT assay. Autophagy was detected by the formation of mRFP-GFP-LC3 fluorescence puncta and observed using transmission electron microscopy, while flow cytometry was employed to detect apoptosis. The protein expressions were detected through Western blotting. Results: CLE-10 induced pro-death autophagy and apoptosis in MDA-MB-231 cells by increasing the protein expression of LC3-II, p-ULK1, Bax, and Bad, as well as downregulating p-PI3K, p-Akt, p-mTOR, p62, LC3-I, Bcl-2, and Bcl-xl. CLE-10 that was pretreated with 3-methyladenine (3-MA) or chloroquine (CQ) weakened the upregulation of the protein expression of p-ULK1, or the downregulation of p62, p-mTOR, and decreased the level of cytotoxicity against MDA-MB-231 cells. Meanwhile, rapamycin enhanced the effect of CLE-10 on the expression of autophagy-related protein and its cytotoxicity, with the IC50 value of CLE-10 decreasing from 4.07 µM to 2.38 µM. Conclusion: CLE-10 induced pro-death autophagy and apoptosis in MDA-MB-231 cells by upregulating the protein expressions of LC3-II, p-ULK1, Bax, and Bad and downregulating p-PI3K, p-Akt, p-mTOR, p62, Bcl-2, and Bcl-xl.
Biological Evaluation and Molecular Docking Studies of Dimethylpyridine Derivatives
Authors: Świątek Piotr , Gębczak Katarzyna , Gębarowski Tomasz , Urniaz Rafal
Published: March 2019

Cyclooxygenase inhibitors as anti-inflammatory agents can be used in chemoprevention. Many in vitro and in vivo studies on human and animal models have explained the mechanisms of the chemopreventive effect of COX inhibitors such as: induction of apoptosis, inhibition of neoplasia, angiogenesis suppression, induction of cell cycle inhibition and inhibition of the expression of peroxisome proliferator-activated receptors. Here, biological evaluation of twelve different Schiff base derivatives of N-(2-hydrazine-2-oxoethyl)-4,6-dimethyl-2-sulfanylpyridine- 3-carboxamide are presented. Their in vitro anti-COX-1/COX-2, antioxidant and anticancer activities were studied. The molecular docking study was performed in order to understand the binding interaction of compounds in the active site of cyclooxygenases. Compounds PS18 and PS33 showed a significant inhibitory activity on COX-1 at lower concentrations compared to meloxicam and piroxicam. The IC50 of COX-1 of these compounds was 57.3 µM for PS18 and 51.8 µM for PS33. Out of the tested compounds, the highest therapeutic index was demonstrated by PS18, PS19, PS33, PS40 and PS41. Lower molar concentrations of these compounds inhibit the growth of cancer cells while not inhibiting the healthy cells. Compounds PS18, PS19 and PS33 simultaneously demonstrated a statistically-significant inhibition of COX-1 or COX-2. This opens up the possibility of applying these compounds in the chemoprevention of cancer.
Toll-Like Receptor-Mediated Recognition of Nucleic Acid Nanoparticles (NANPs) in Human Primary Blood Cells
Authors: Hong Enping , Halman Justin R. , Shah Ankit , Cedrone Edward , Truong Nguyen , Afonin Kirill A. , Dobrovolskaia Marina A.
Published: March 2019

Infusion reactions (IRs) create a translational hurdle for many novel therapeutics, including those utilizing nanotechnology. Nucleic acid nanoparticles (NANPs) are a novel class of therapeutics prepared by rational design of relatively short oligonucleotides to self-assemble into various programmable geometric shapes. While cytokine storm, a common type of IR, has halted clinical development of several therapeutic oligonucleotides, NANP technologies hold tremendous potential to bring these reactions under control by tuning the particle’s physicochemical properties to the desired type and magnitude of the immune response. Recently, we reported the very first comprehensive study of the structure–activity relationship between NANPs’ shape, size, composition, and their immunorecognition in human cells, and identified the phagolysosomal pathway as the major route for the NANPs’ uptake and subsequent immunostimulation. Here, we explore the molecular mechanism of NANPs’ recognition by primary immune cells, and particularly the contributing role of the Toll-like receptors. Our current study expands the understanding of the immune recognition of engineered nucleic acid-based therapeutics and contributes to the improvement of the nanomedicine safety profile.
Defining Processing Times for Accelerator Produced 225Ac and Other Isotopes from Proton Irradiated Thorium
Authors: Fitzsimmons Jonathan , Griswold Justin , Medvedev Dmitri , Cutler Cathy S. , Mausner Leonard
Published: March 2019

During the purification of radioisotopes, decay periods or time dependent purification steps may be required to achieve a certain level of radiopurity in the final product. Actinum-225 (Ac-225), Silver-111 (Ag-111), Astatine-211 (At-211), Ruthenium-105 (Ru-105), and Rhodium-105 (Rh-105) are produced in a high energy proton irradiated thorium target. Experimentally measured cross sections, along with MCNP6-generated cross sections, were used to determine the quantities of Ac-225, Ag-111, At-211, Ru-105, Rh-105, and other co-produced radioactive impurities produced in a proton irradiated thorium target at Brookhaven Linac Isotope Producer (BLIP). Ac-225 and Ag-111 can be produced with high radiopurity by the proton irradiation of a thorium target at BLIP.
Oil-in-Water Emulsions Stabilized by Ultrasonic Degraded Polysaccharide Complex
Authors: Li Yujie , Xiang Dong , Wang Bo , Gong Xiaoyue
Published: March 2019

The effects of ultrasound on the molecular weight distribution and emulsifying properties of both xanthan gum (XG) and propylene glycol alginate (PGA) were investigated. The results showed that ultrasonic treatment at different intensities decreased the apparent viscosity and narrowed the molecular weight distribution. Higher intensity increased the effectivity of the sonochemical effect. Ultrasound degradation did not change the primary structure of the PGA-XG complex, and SEM analysis showed that the morphology of the original polysaccharide differed from that of the degraded polysaccharide fractions. The ultrasonic intensities and treatment times had a substantial influence on the stability of the polysaccharide-stabilized oil-in-water (O/W) emulsions. The O/W emulsion stabilized by the polysaccharide treated with 270 W ultrasound waves for 7 min led to the smallest average particle size (detected via fluorescence microscopy) and showed stability against aggregation in O/W emulsions.
Thermal Conductivity of Defective Graphene Oxide: A Molecular Dynamic Study
Authors: Yang Yi , Cao Jing , Wei Ning , Meng Donghui , Wang Lina , Ren Guohua , Yan Rongxin , Zhang Ning
Published: March 2019

In this paper, the thermal properties of graphene oxide (GO) with vacancy defects were studied using a non-equilibrium molecular dynamics method. The results showed that the thermal conductivity of GO increases with the model length. A linear relationship of the inverse length and inverse thermal conductivity was observed. The thermal conductivity of GO decreased monotonically with an increase in the degree of oxidation. When the degree of oxidation was 10%, the thermal conductivity of GO decreased by ~90% and this was almost independent of chiral direction. The effect of vacancy defect on the thermal conductivity of GO was also considered. The size effect of thermal conductivity gradually decreases with increasing defect concentration. When the vacancy defect ratio was beyond 2%, the thermal conductivity did not show significant change with the degree of oxidation. The effect of vacancy defect on thermal conductivity is greater than that of oxide group concentration. Our results can provide effective guidance for the designed GO microstructures in thermal management and thermoelectric applications.
Anti-Oxidative and Anti-Aging Activities of Porcine By-Product Collagen Hydrolysates Produced by Commercial Proteases: Effect of Hydrolysis and Ultrafiltration
Authors: Hong Geun-Pyo , Min Sang-Gi , Jo Yeon-Ji
Published: March 2019

To investigate methods for improving the processing of porcine waste, porcine skin was hydrolyzed using different commercially available proteases (Alcalase, Flavorzyme, Neutrase, Bromeline, Protamex, and Papain) under several optimal conditions. Following enzymatic hydrolysis, the collagen hydrolysates (CHs) were fractionated by molecular weight (3 kDa) via membrane ultrafiltration. The CHs were analyzed for physical properties (pH, protein recovery, free amino group content, molecular weight distribution, and amino composition) as well as for functional properties (antioxidant activities and anti-aging activities). Among the CHs, CHs hydrolyzed by Alcalase (CH-Alcalase) exhibited the highest degree of hydrolysis compared to other CHs. Both “CH-Alcalase” and “CH-Alcalase < 3 kDa” fractions showed a considerably high antioxidant activity and collagenase inhibition activity. Therefore, resulting bioactives have potential for development as antioxidants and anti-aging ingredients in the food, cosmetics, and pharmaceuticals, from animal by-products.
Autofluorescence Imaging Reflects the Nuclear Enlargement of Tumor Cells as well as the Cell Proliferation Ability and Aberrant Status of the p53, Ki-67, and p16 Genes in Colon Neoplasms
Authors: Moriichi Kentaro , Fujiya Mikihiro , Kobayashi Yu , Murakami Yuki , Iwama Takuya , Kunogi Takehito , Sasaki Takahiro , Ijiri Masami , Takahashi Keitaro , Tanaka Kazuyuki , Sakatani Aki , Ando Katsuyoshi , Nomura Yoshiki , Ueno Nobuhiro , Kashima Shin , Ikuta Katsuya , Tanabe Hiroki , Mizukami Yusuke , Saitoh Yusuke , Okumura Toshikatsu
Published: March 2019

Background: Autofluorescence imaging (AFI) is useful for diagnosing colon neoplasms, but what affects the AFI intensity remains unclear. This study investigated the association between AFI and the histological characteristics, aberrant methylation status, and aberrant expression in colon neoplasms. Methods: Fifty-three patients with colorectal neoplasms who underwent AFI were enrolled. The AFI intensity (F index) was compared with the pathological findings and gene alterations. The F index was calculated using an image analysis software program. The pathological findings were assessed by the tumor crypt density, cell densities, and N/C ratio. The aberrant methylation of p16, E-cadherin, Apc, Runx3, and hMLH1 genes was determined by a methylation-specific polymerase chain reaction. The aberrant expression of p53 and Ki-67 was evaluated by immunohistochemical staining. Results: An increased N/C ratio, the aberrant expression of p53, Ki-67, and the altered methylation of p16 went together with a lower F index. The other pathological findings and the methylation status showed no association with the F index. Conclusions: AFI reflects the nuclear enlargement of tumor cells, the cell proliferation ability, and the altered status of cell proliferation-related genes, indicating that AFI is a useful and practical method for predicting the dysplastic grade of tumor cells and cell proliferation.
Design and Synthesis of Matrine Derivatives as Novel Anti-Pulmonary Fibrotic Agents via Repression of the TGFβ/Smad Pathway
Authors: Li Lingyu , Ma Liyan , Wang Dongchun , Jia Hongmei , Yu Meng , Gu Yucheng , Shang Hai , Zou Zhongmei
Published: March 2019

A total of 18 matrine derivatives were designed, synthesized, and evaluated for their inhibitory effect against TGF-β1-induced total collagen accumulation in human fetal lung fibroblast MRC-5 cell lines. Among them, compound 3f displayed the most potent anti-fibrotic activity (IC50 = 3.3 ± 0.3 μM) which was 266-fold more potent than matrine. 3f significantly inhibited the fibroblast-to-myofibroblast transition and extracellular matrix production of MRC-5 cells. The TGF-β/small mothers against decapentaplegic homologs (Smad) signaling was also inhibited by 3f, as evidenced by inhibition of cytoplasm-to-nuclear translocation of Smad2/3 and suppression of TGF-β1-induced upregulation of TGF-β receptor type I (TGFβRI). Additionally, 3f exhibited potent inhibitory effects against TGF-β1-induced fibroblasts migration. These data suggested that 3f might be a potential agent for the treatment of idiopathic pulmonary fibrosis via repression of the TGFβ/Smad signaling pathway.
Preparation of Sesquiterpene Lactone Derivatives: Cytotoxic Activity and Selectivity of Action
Authors: Beer María F. , Bivona Augusto E. , Sánchez Alberti Andrés , Cerny Natacha , Reta Guillermo F. , Martín Víctor S. , Padrón José M. , Malchiodi Emilio L. , Sülsen Valeria P. , Donadel Osvaldo J.
Published: March 2019

Cancer is one of the most important causes of death worldwide. Solid tumors represent the great majority of cancers (>90%) and the chemotherapeutic agents used for their treatment are still characterized by variable efficacy and toxicity. Sesquiterpene lactones are a group of naturally occurring compounds that have displayed a diverse range of biological activities including cytotoxic activity. A series of oxygenated and oxy-nitrogenated derivatives (4–15) from the sesquiterpene lactones cumanin (1), helenalin (2), and hymenin (3) were synthesized. The silylated derivatives of helenalin, compounds 13 and 14, were found to be the most active against tumor cell lines, with GI50 values ranging from 0.15 to 0.59 μM. The ditriazolyl cumanin derivative (11) proved to be more active and selective than cumanin in the tested breast, cervix, lung, and colon tumor cell lines. This compound was the least toxic against splenocytes (CC50 = 524.1 µM) and exhibited the greatest selectivity on tumor cell lines. This compound showed a GI50 of 2.3 µM and a SI of 227.9 on WiDr human colon tumor cell lines. Thus, compound 11 can be considered for further studies and is a candidate for the development of new antitumor agents.
Metabolic Profiling of Pitaya (Hylocereus polyrhizus) during Fruit Development and Maturation
Authors: Wu Yawei , Xu Juan , He Yizhong , Shi Meiyan , Han Xiumei , Li Wenyun , Zhang Xingwu , Wen Xiaopeng
Published: March 2019

Pitaya (Hylocereus polyrhizus) has attracted much interest from consumers as it is a novelty fruit with high nutrient content and a tolerance to drought stress. As a group of attractive pigment- and health-promoting natural compounds, betalains represent a visual feature for pitaya fruit quality. However, little information on the correlation between betalains and relevant metabolites exists so far. Currently, color (Commission International del’Eclairage, CIE) parameters, betalain contents, and untargeted metabolic profiling (gas chromatography-time-of-flight-mass spectrometry, GC–MS and liquid chromatography tandem mass spectrometry, LC–MS) have been examined on ‘Zihonglong’ fruits at nine different developmental stages, and the variation character of the metabolite contents was simultaneously investigated between peel and pulp. Furthermore, principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were used to explore metabolite profiles from the fruit samples. Our results demonstrated that the decrease of amino acid, accompanied by the increase of sugars and organic acid, might contribute to the formation of betalains. Notably, as one of four potential biomarker metabolites, citramalic acid might be related to betalain formation.
Endogenous and Exogenous Stimuli-Responsive Drug Delivery Systems for Programmed Site-Specific Release
Authors: Raza Ali , Rasheed Tahir , Nabeel Faran , Hayat Uzma , Bilal Muhammad , Iqbal Hafiz M. N.
Published: March 2019

In this study, we reviewed state-of-the-art endogenous-based and exogenous-based stimuli-responsive drug delivery systems (DDS) for programmed site-specific release to overcome the drawbacks of conventional therapeutic modalities. This particular work focuses on the smart chemistry and mechanism of action aspects of several types of stimuli-responsive polymeric carriers that play a crucial role in extracellular and intracellular sections of diseased tissues or cells. With ever increasing scientific knowledge and awareness, research is underway around the globe to design new types of stimuli (external/internal) responsive polymeric carriers for biotechnological applications at large and biomedical and/or pharmaceutical applications, in particular. Both external/internal and even dual/multi-responsive behavior of polymeric carriers is considered an essential element of engineering so-called ‘smart’ DDS, which controls the effective and efficient dose loading, sustained release, individual variability, and targeted permeability in a sophisticated manner. So far, an array of DDS has been proposed, developed, and implemented. For instance, redox, pH, temperature, photo/light, magnetic, ultrasound, and electrical responsive DDS and/or all in all dual/dual/multi-responsive DDS (combination or two or more from any of the above). Despite the massive advancement in DDS arena, there are still many challenging concerns that remain to be addressed to cover the research gap. In this context, herein, an effort has been made to highlight those concerning issues to cover up the literature gap. Thus, the emphasis was given to the drug release mechanism and applications of endogenous and exogenous based stimuli-responsive DDS in the clinical settings.
Zinc Porphyrin-Functionalized Fullerenes for the Sensitization of Titania as a Visible-Light Active Photocatalyst: River Waters and Wastewaters Remediation
Authors: Regulska Elzbieta , Rivera-Nazario Danisha Maria , Karpinska Joanna , Plonska-Brzezinska Marta Eliza , Echegoyen Luis
Published: March 2019

Zinc porphyrin-functionalized fullerene [C60] derivatives have been synthesized and used to prepare titania-based composites. The electrochemical properties and HOMO and LUMO levels of the photosensitizers were determined by electrochemical measurements. Raman and IR techniques were used to study chemical groups present on the titania surface. Absorption properties of the composites were measured in the solid state by diffuse reflectance UV-Vis spectra (DRS). The zeta potential and aggregate sizes were determined using dynamic light scattering (DLS) and electrophoretic light scattering (ELS) techniques. Surface areas were estimated based on Brunauer–Emmett–Teller (BET) isotherms. The photocatalytic activity of the photocatalysts was tested using two model pollutants, phenol and methylene blue. The composite with the highest photocatalytic potential (1/TiO2) was used for river and wastewater remediation. The photodegradation intermediates were identified by LC-UV/Vis-MS/MS techniques.
Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application
Authors: Xu Dong , Hu Meng-Jiao , Wang Yan-Qiu , Cui Yuan-Lu
Published: March 2019

Quercetin is a bioactive compound that is widely used in botanical medicine and traditional Chinese medicine due to its potent antioxidant activity. In recent years, antioxidant activities of quercetin have been studied extensively, including its effects on glutathione (GSH), enzymatic activity, signal transduction pathways, and reactive oxygen species (ROS) caused by environmental and toxicological factors. Chemical studies on quercetin have mainly focused on the antioxidant activity of its metal ion complexes and complex ions. In this review, we highlight the recent advances in the antioxidant activities, chemical research, and medicinal application of quercetin.
Electric Properties of Molecule Zr2Fe Based on the Full Relativistic Theory
Authors: Song Jiangfeng , Zhang Li , Kong Xianggang , Hu Xiaoyu , Meng Daqiao , Zhu Zhenghe
Published: March 2019

The present work is devoted to the study of the electric properties: electric dipole moment, electric quadrupole moment, electric field gradients and electric dipole polarizability of molecule Zr2Fe on base of the full relativistic theory with basis set 3–21G. The electric dipole moment of Zr2Fe is symmetrical to the axis of C 2 V —the vector sum of two projections for two chemical bond FeZr (3.2883 Å), based on when there is charge distribution. The force constant k 2 is directly connected with electric field gradients.
CtACO1 Overexpression Resulted in the Alteration of the Flavonoids Profile of Safflower
Authors: Tu Yanhua , He Beixuan , Gao Songyan , Guo Dandan , Jia Xinlei , Dong Xin , Guo Meili
Published: March 2019

Background: Flavonoids with various structures play a vital role in plant acclimatization to varying environments as well as in plant growth, development, and reproduction. Exogenous applications of ethylene and 1-aminocyclopropane carboxylic acid (ACC), could affect the accumulation of flavonoids. Very few attempts have been made to investigate the effect of 1-aminocyclopropane carboxylic acid oxidase (ACO), a unique enzyme that catalyzes ACC to ethylene, on genes and metabolites in the flavonoid biosynthetic pathway. In this study, two ACOs in safflower (CtACOs) were cloned, and then transgenic safflower with overexpressed CtACO1 was generated through the Agrobacterium-mediated floral dipping method. Results: CtACO1 and CtACO2 were both characterized by the 2-oxoglutarate binding domain RxS and the ferrous iron binding site HxDxnH as ACOs from other plants. However, the transcript levels of CtACO1 in flowers at stages I, II, III, and IV were all higher than those of CtACO2. At the cellular level, by using electroporation transformation, CtACO1 was found to be localized at the cytomembrane in onion epidermal cells. CtACO1 overexpression had varying effects on genes involved in the ethylene and flavonoid biosynthetic pathways. The metabolites analysis showed that CtACO1 overexpression lines had a higher accumulation of quercetin and its glycosylated derivatives (quercetin 3-β-d-glucoside and rutin). In contrast, the accumulation of quinochalcones (hydroxysafflor yellow A and carthamin), kaempferol glycosylated derivatives (kaempferol-3-O-β-rutinoside and kaempferol-3-O-β-d-glucoside), apigenin, and luteolin in CtACO1 overexpression lines were decreased. Conclusion: This study confirmed the feasibility of applying the floral dipping method to safflower and showed a novel regulatory effect of CtACO1 in the flavonoid biosynthetic pathway. It provides hypothetical and practical groundwork for further research on regulating the overall metabolic flux of flavonoids in safflower, particularly hydroxysafflor yellow A and other quinochalcones, by using appropriate genetic engineering strategies.
Antiviral Activity of Uridine Derivatives of 2-Deoxy Sugars against Tick-Borne Encephalitis Virus
Authors: Krol Ewelina , Wandzik Ilona , Brzuska Gabriela , Eyer Luděk , Růžek Daniel , Szewczyk Boguslaw
Published: March 2019

Tick-borne encephalitis virus (TBEV) is a causative agent of tick-borne encephalitis (TBE), one of the most important human infections involving the central nervous system. Although effective vaccines are available on the market, they are recommended only in endemic areas. Despite many attempts, there are still no specific antiviral therapies for TBEV treatment. Previously, we synthesized a series of uridine derivatives of 2-deoxy sugars and proved that some compounds show antiviral activity against viruses from the Flaviviridae and Orthomyxoviridae families targeting the late steps of the N-glycosylation process, affecting the maturation of viral proteins. In this study, we evaluated a series of uridine derivatives of 2-deoxy sugars for their antiviral properties against two strains of the tick-borne encephalitis virus; the highly virulent TBEV strain Hypr and the less virulent strain Neudoerfl. Four compounds (2, 4, 10, and 11) showed significant anti-TBEV activity with IC50 values ranging from 1.4 to 10.2 µM and low cytotoxicity. The obtained results indicate that glycosylation inhibitors, which may interact with glycosylated membrane TBEV E and prM proteins, might be promising candidates for future antiviral therapies against TBEV.
Autophagy in Crotonaldehyde-Induced Endothelial Toxicity
Authors: Lee Seung Eun , Park Hye Rim , Park Cheung-Seog , Ahn Hyun-Jong , Cho Jeong-Je , Lee Jongsung , Park Yong Seek
Published: March 2019

Crotonaldehyde is an extremely toxic α,β-unsaturated aldehyde found in cigarette smoke, and it causes inflammation and vascular dysfunction. Autophagy has been reported to play a key role in the pathogenesis of vascular diseases. However, the precise mechanism underlying the role of acute exposure crotonaldehyde in vascular disease development remains unclear. In the present study, we aimed to investigate the effect of crotonaldehyde-induced autophagy in endothelial cells. Acute exposure to crotonaldehyde decreased cell viability and induced autophagy followed by cell death. In addition, inhibiting the autophagic flux markedly promoted the viability of endothelial cells exposed to high concentrations of crotonaldehyde. Crotonaldehyde activated the AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (MAPK) pathways, and pretreatment with inhibitors specific to these kinases showed autophagy inhibition and partial improvement in cell viability. These data show that acute exposure to high concentrations of crotonaldehyde induces autophagy-mediated cell death. These results might be helpful to elucidate the mechanisms underlying crotonaldehyde toxicity in the vascular system and contribute to environmental risk assessment.
Solid Lipid Nanoparticles Surface Modification Modulates Cell Internalization and Improves Chemotoxic Treatment in an Oral Carcinoma Cell Line
Authors: Arana Lide , Bayón-Cordero Laura , Sarasola Laura Isabel , Berasategi Miren , Ruiz Sandra , Alkorta Itziar
Published: March 2019

Solid lipid nanoparticles (SLN) present low toxicity, versatility to incorporate both lipophilic and hydrophilic drugs, controlled drug release and they are easy to scale-up. It is well known that the endocytosis pathway by which SLN are taken up and the subsequent subcellular distribution are crucial for the biological effect of the incorporated drug. In addition, interactions between SLN and cells depend on many factors, such as, the composition of nanoparticle surface. In this work different amounts of phosphatidylethanolamine polyethylene glycol (PE–PEG) were added to SLN composed of stearic acid, Epikuron 200 and sodium taurodeoxycholate. Characterization of obtained nanoparticle suspensions were performed by the analysis of particle size, polydispersity index, ζ-potential, cell toxicity and cell internalization pathway. We have observed that the presence of PE–PEG improves active cell internalization of the nanoparticles in an oral adenocarcinoma cell line, reducing non-specific internalization mechanisms. Finally, we have tested the effect of surface coating on the efficiency of incorporated drugs using all-trans retinoic acid as a model drug. We have observed that delivery of this drug into PE–PEG coated SLN increases its chemotoxic effect compared to non-coated SLN. Therefore, it can be concluded that surface modification with PE–PEG improves the efficiency and the specificity of the SLN-loaded drug.
One-Step Hydrothermal Synthesis of Yellow and Green Emitting Silicon Quantum Dots with Synergistic Effect
Authors: Zhang Zhixia , Wei Chunjin , Ma Wenting , Li Jun , Xiao Xincai , Zhao Dan
Published: March 2019

The concept of synergistic effects has been widely applied in many scientific fields such as in biomedical science and material chemistry, and has further attracted interest in the fields of both synthesis and application of nanomaterials. In this paper, we report the synthesis of long-wavelength emitting silicon quantum dots based on a one-step hydrothermal route with catechol (CC) and sodium citrate (Na-citrate) as a reducing agent pair, and N-[3-(trimethoxysilyl)propyl]ethylenediamine (DAMO) as silicon source. By controlling the reaction time, yellow-emitting silicon quantum dots and green-emitting silicon quantum dots were synthesized with quantum yields (QYs) of 29.4% and 38.3% respectively. The as-prepared silicon quantum dots were characterized by fluorescence (PL) spectrum, UV–visible spectrum, high resolution transmission electron microscope (HRTEM), Fourier transform infrared (FT-IR) spectrometry energy dispersive spectroscopy (EDS), and Zeta potential. With the aid of these methods, this paper further discussed how the optical performance and surface characteristics of the prepared quantum dots (QDs) influence the fluorescence mechanism. Meanwhile, the cell toxicity of the silicon quantum dots was tested by the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium (MTT) bromide method, and its potential as a fluorescence ink explored. The silicon quantum dots exhibit a red-shift phenomenon in their fluorescence peak due to the participation of the carbonyl group during the synthesis. The high-efficiency and stable photoluminescence of the long-wavelength emitting silicon quantum dots prepared through a synergistic effect is of great value in their future application as novel optical materials in bioimaging, LED, and materials detection.
MicroRNA Shuttle from Cell-To-Cell by Exosomes and Its Impact in Cancer
Authors: Schwarzenbach Heidi , Gahan Peter B.
Published: March 2019

The identification of exosomes, their link to multivesicular bodies and their potential role as a messenger vehicle between cancer and healthy cells opens up a new approach to the study of intercellular signaling. Furthermore, the fact that their main cargo is likely to be microRNAs (miRNAs) provides the possibility of the transfer of such molecules to control activities in the recipient cells. This review concerns a brief overview of the biogenesis of both exosomes and miRNAs together with the movement of such structures between cells. The possible roles of miRNAs in the development and progression of breast, ovarian and prostate cancers are discussed.
PHAGE Study: Effects of Supplemental Bacteriophage Intake on Inflammation and Gut Microbiota in Healthy Adults
Authors: Febvre Hallie P. , Rao Sangeeta , Gindin Melinda , Goodwin Natalie D. M. , Finer Elijah , Vivanco Jorge S. , Lu Shen , Manter Daniel K. , Wallace Taylor C. , Weir Tiffany L.
Published: March 2019

The gut microbiota is increasingly recognized as an important modulator of human health. As such, there is a growing need to identify effective means of selectively modifying gut microbial communities. Bacteriophages, which were briefly utilized as clinical antimicrobials in the early 20th century, present an opportunity to selectively reduce populations of undesirable microorganisms. However, whether intentional consumption of specific bacteriophages affects overall gut ecology is not yet known. Using a commercial cocktail of Escherichia coli-targeting bacteriophages, we examined their effects on gut microbiota and markers of intestinal and systemic inflammation in a healthy human population. In a double-blinded, placebo-controlled crossover trial, normal to overweight adults consumed bacteriophages for 28 days. Stool and blood samples were collected and used to examine inflammatory markers, lipid metabolism, and gut microbiota. Reductions in fecal E. coli loads were observed with phage consumption. However, there were no significant changes to alpha and beta diversity parameters, suggesting that consumed phages did not globally disrupt the microbiota. However, specific populations were altered in response to treatment, including increases in members of the butyrate-producing genera Eubacterium and a decreased proportion of taxa most closely related to Clostridium perfringens. Short-chain fatty acid production, inflammatory markers, and lipid metabolism were largely unaltered, but there was a small but significant decrease in circulating interleukin-4 (Il-4). Together, these data demonstrate the potential of bacteriophages to selectively reduce target organisms without global disruption of the gut community.
Letter to the Editor Re: Oh J., et al. Nutrients 2019, 11, 343
Authors: Hernández-Garduño Eduardo
Published: March 2019

To the editor, [...]
Predicting Real-Life Eating Behaviours Using Single School Lunches in Adolescents
Authors: Langlet Billy , Fagerberg Petter , Delopoulos Anastasios , Papapanagiotou Vasileios , Diou Christos , Maramis Christos , Maglaveras Nikolaos , Anvret Anna , Ioakimidis Ioannis
Published: March 2019

Large portion sizes and a high eating rate are associated with high energy intake and obesity. Most individuals maintain their food intake weight (g) and eating rate (g/min) rank in relation to their peers, despite food and environmental manipulations. Single meal measures may enable identification of “large portion eaters” and “fast eaters,” finding individuals at risk of developing obesity. The aim of this study was to predict real-life food intake weight and eating rate based on one school lunch. Twenty-four high-school students with a mean (±SD) age of 16.8 yr (±0.7) and body mass index of 21.9 (±4.1) were recruited, using no exclusion criteria. Food intake weight and eating rate was first self-rated (“Less,” “Average” or “More than peers”), then objectively recorded during one school lunch (absolute weight of consumed food in grams). Afterwards, subjects recorded as many main meals (breakfasts, lunches and dinners) as possible in real-life for a period of at least two weeks, using a Bluetooth connected weight scale and a smartphone application. On average participants recorded 18.9 (7.3) meals during the study. Real-life food intake weight was 327.4 g (±110.6), which was significantly lower (p = 0.027) than the single school lunch, at 367.4 g (±167.2). When the intra-class correlation of food weight intake between the objectively recorded real-life and school lunch meals was compared, the correlation was excellent (R = 0.91). Real-life eating rate was 33.5 g/min (±14.8), which was significantly higher (p = 0.010) than the single school lunch, at 27.7 g/min (±13.3). The intra-class correlation of the recorded eating rate between real-life and school lunch meals was very large (R = 0.74). The participants’ recorded food intake weights and eating rates were divided into terciles and compared between school lunches and real-life, with moderate or higher agreement (κ = 0.75 and κ = 0.54, respectively). In contrast, almost no agreement was observed between self-rated and real-life recorded rankings of food intake weight and eating rate (κ = 0.09 and κ = 0.08, respectively). The current study provides evidence that both food intake weight and eating rates per meal vary considerably in real-life per individual. However, based on these behaviours, most students can be correctly classified in regard to their peers based on single school lunches. In contrast, self-reported food intake weight and eating rate are poor predictors of real-life measures. Finally, based on the recorded individual variability of real-life food intake weight and eating rate, it is not advised to rank individuals based on single recordings collected in real-life settings.
Canadian Children from Food Insecure Households Experience Low Self-Esteem and Self-Efficacy for Healthy Lifestyle Choices
Authors: Godrich Stephanie L. , Loewen Olivia K. , Blanchet Rosanne , Willows Noreen , Veugelers Paul
Published: March 2019

The objectives of this cross-sectional study were to: (i) determine whether there are differences in self-esteem and self-efficacy for healthy lifestyle choices between children living in food secure and food insecure households; and (ii) determine whether the association between household food insecurity (HFI), self-esteem and self-efficacy differs by gender. Survey responses of 5281 fifth-grade students (10 and 11 years of age) participating in the Canadian Children’s Lifestyle and School Performance Study II were analyzed using logistic and linear regression. HFI status was determined by the six-item short-form Household Food Security Survey Module (HFSSM). Students from food insecure households had significantly higher odds of low self-esteem, and significantly lower scores for global self-efficacy to make healthy choices, compared to students from food secure households. These associations were stronger for girls than for boys and appeared independent of parental educational attainment. Household income appeared to be the essential underlying determinant of the associations of food insecurity with self-esteem and self-efficacy. Upstream social policies such as improving the household income of low-income residents will reduce food insecurity and potentially improve self-esteem and self-efficacy for healthy choices among children. This may improve health and learning, and in the long term, job opportunities and household earnings.
Impact of Nutritional Changes on Nonalcoholic Fatty Liver Disease
Authors: Perdomo Carolina M. , Frühbeck Gema , Escalada Javier
Published: March 2019

Non-alcoholic fatty liver disease (NAFLD) is a major global health threat due to its growing incidence and prevalence. It is becoming the leading cause of liver disease in addition to its strong association with cardio-metabolic disease. Therefore, its prevention and treatment are of strong public interest. Therapeutic approaches emphasize lifestyle modifications including physical activity and the adoption of healthy eating habits that intend to mainly control body weight and cardio-metabolic risk factors associated with the metabolic syndrome. Lifestyle interventions may be reinforced by pharmacological treatment in advanced stages, though there is still no registered drug for the specific treatment of NAFLD. The purpose of this review is to assess the evidence available regarding the impact of dietary recommendations against NAFLD, highlighting the effect of macronutrient diet composition and dietary patterns in the management of NAFLD.
LC478, a Novel Di-Substituted Adamantyl Derivative, Enhances the Oral Bioavailability of Docetaxel in Rats
Authors: Han Seung Yon , Lu Qili , Lee Kyeong , Choi Young Hee
Published: March 2019

P-glycoprotein (P-gp)-mediated efflux of docetaxel in the gastrointestinal tract mainly impedes its oral chemotherapy. Recently, LC478, a novel di-substituted adamantyl derivative, was identified as a non-cytotoxic P-gp inhibitor in vitro. Here, we assessed whether LC478 enhances the oral bioavailability of docetaxel in vitro and in vivo. LC478 inhibited P-gp mediated efflux of docetaxel in Caco-2 cells. In addition, 100 mg/kg of LC478 increased intestinal absorption of docetaxel, which led to an increase in area under plasma concentration-time curve (AUC) and absolute bioavailability of docetaxel in rats. According to U.S. FDA criteria (I, an inhibitor concentration in vivo tissue)/(IC50, inhibitory constant in vitro) >10 determines P-gp inhibition between in vitro and in vivo. The values 15.6–20.5, from (LC478 concentration in intestine, 9.37–12.3 μM)/(IC50 of LC478 on P-gp inhibition in Caco-2 cell, 0.601 μM) suggested that 100 mg/kg of LC478 sufficiently inhibited P-gp to enhance oral absorption of docetaxel. Moreover, LC478 inhibited P-gp mediated efflux of docetaxel in the ussing chamber studies using rat small intestines. Our study demonstrated that the feasibility of LC478 as an ideal enhancer of docetaxel bioavailability by P-gp inhibition in dose (concentration)-dependent manners.
Development and Evaluation of Poorly Water-Soluble Celecoxib as Solid Dispersions Containing Nonionic Surfactants Using Fluidized-Bed Granulation
Authors: Kwon Hyeok Jin , Heo Eun-Ji , Kim Young-Hwan , Kim Sarah , Hwang Young-Ha , Byun Ji-Mi , Cheon Se Hyeop , Park Sang Yeob , Kim Dong Yun , Cho Kwan Hyung , Maeng Han-Joo , Jang Dong-Jin
Published: March 2019

The purpose of this study is to develop a solid dispersion system with improved dissolution, absorption, and patient compliance of poorly water-soluble celecoxib (CXB). Instead of sodium lauryl sulfate (SLS), an anionic surfactant used in the marketed product (Celebrex®), solubilization was performed using non-ionic surfactants with low toxicity. Cremophor RH40 (Cre-RH) was selected as the optimal solubilizer. Granules and tablets containing CXB and Cre-RH were prepared via fluid-bed and tableting processes, respectively. The morphology, crystallinity, flowability, dissolution, and pharmacokinetics for CXB-solid dispersion granules (SDGs) and the hardness and friability for CXB-solid dispersion tablets (SDTs) were evaluated. The solubility of CXB was found to be increased by about 717-fold when using Cre-RH. The dissolution of granules containing Cre-RH was found to be increased greatly compared with CXB API and Celebrex® (66.9% versus 2.3% and 37.2% at 120 min). The improvement of the dissolution was confirmed to be the same as that of granules in tablets. The CXB formulation resulted in 4.6- and 4.9-fold higher AUCinf and Cmax of CXB compared with those of an oral dose of CXB powder in rats. In short, these data suggest that the solid dispersion based on Cre-RH—a non-toxic solubilizer, non-ionic surfactant— may be an effective formulation for CXB to enhance its oral bioavailability and safety.
Tenofovir Hot-Melt Granulation using Gelucire® to Develop Sustained-Release Vaginal Systems for Weekly Protection against Sexual Transmission of HIV
Authors: Notario-Pérez Fernando , Cazorla-Luna Raúl , Martín-Illana Araceli , Ruiz-Caro Roberto , Peña Juan , Veiga María-Dolores
Published: March 2019

Hot-melt granulation is a technique used to obtain granules by dispersing a drug in polymers at a high temperature. Tenofovir, an antiretroviral drug with proven activity as a vaginal microbicide, was dispersed in melted Gelucire® (or a mixture of different Gelucire®) to obtain drug-loaded granules. Studies performed on the granules proved that the drug is not altered in the hot-melt granulation process. The granules obtained were included in a matrix formed by the hydrophilic polymers hydroxypropylmethylcellulose and chitosan to obtain vaginal tablets that combine different mechanisms of controlled release: The Gelucire® needs to soften to allow the release of the Tenofovir, and the hydrophilic polymers must form a gel so the drug can diffuse through it. The studies performed with the tablets were swelling behavior, Tenofovir release, and ex vivo mucoadhesion. The tablets containing granules obtained with Tenofovir and Gelucire® 43/01 in a ratio of 1:2 in a matrix formed by hydroxypropylmethylcellulose and chitosan in a ratio of 1.9:1 were selected as the optimal formulation, since they release Tenofovir in a sustained manner over 216h and remain attached to the vaginal mucosa throughout. A weekly administration of these tablets would therefore offer women protection against the sexual transmission of HIV.
A Computationally Assisted Ar I Emission Line Ratio Technique to Infer Electron Energy Distribution and Determine Other Plasma Parameters in Pulsed Low-Temperature Plasma
Authors: Franek James B. , Nogami Samuel H. , Koepke Mark E. , Demidov Vladimir I. , Barnat Edward V.
Published: March 2019

In the post-transient stage of a 1-Torr pulsed argon discharge, a computationally assisted diagnostic technique is demonstrated for either inferring the electron energy distribution function (EEDF) if the metastable-atom density is known (i.e., measured) or quantitatively determining the metastable-atom density if the EEDF is known. This technique, which can be extended to be applicable to the initial and transient stages of the discharge, is based on the sensitivity of both emission line ratio values to metastable-atom density, on the EEDF, and on correlating the measurements of metastable-atom density, electron density, reduced electric field, and the ratio of emission line pairs (420.1–419.8 nm or 420.1–425.9 nm) for a given expression of the EEDF, as evidenced by the quantitative agreement between the observed emission line ratio and the predicted emission line ratio. Temporal measurement of electron density, metastable-atom density, and reduced electric field are then used to infer the transient behavior of the excitation rates describing electron-atom collision-induced excitation in the pulsed positive column. The changing nature of the EEDF, as it starts off being Druyvesteyn and becomes more Maxwellian later with the increasing electron density, is key to interpreting the correlation and explaining the temporal behavior of the emission line ratio in all stages of the discharge. Similar inferences of electron density and reduced electric field based on readily available diagnostic signatures may also be afforded by this model.
MgAl-Layered-Double-Hydroxide/Sepiolite Composite Membrane for High-Performance Water Treatment Based on Layer-by-Layer Hierarchical Architectures
Authors: Yu Zongxue , Li Xiuhui , Peng Yixin , Min Xia , Yin Di , Shao Liangyan
Published: March 2019

One of the major challenges in the removal of organic pollutants is to design a material with high efficiency and high flux that can remove both cationic and anionic dyes, oil-in-water (O/W) emulsion and heavy metal ions. Herein, we constructed novel chemically stabilized MgAl-layered-double-hydroxide/sepiolite (MgAl-LDH/Sep) composite membranes via 3D hierarchical architecture construction methods. These membranes were analyzed by scanning electron microscopy (SEM), atomic force microscopy (AFM) and X-ray diffraction (XRD), etc. Benefiting from the presence of hydrophilic functional groups on the surface of the film, the membranes show an enhanced water flux (~1200 L·m−2 h−1), while keeping a high dyes rejection (above 99.8% for anionic and cationic dyes). Moreover, the CA membrane coupled with MgAl-LDH/Sep exhibits a multifunctional characteristic for the efficient removal of mesitylene (99.2%), petroleum ether (99.03%), decane (99.07%), kerosene (99.4%) and heavy metal ion in water due to the layer-by-layer sieving. This hierarchical architecture is proved to have excellent environmental and chemical stability. Therefore, the membrane has potential in the treatment of sewage wastewater.
Fabrication of Ultrafine PPS Fibers with High Strength and Tenacity via Melt Electrospinning
Authors: Fan Zuo-Ze , He Hong-Wei , Yan Xu , Zhao Ren-Hai , Long Yun-Ze , Ning Xin
Published: March 2019

Electrospinning (e-spinning) is an emerging technique to prepare ultrafine fibers. Polyphenylene sulfide (PPS) is a high-performance resin which does not dissolve in any solvent at room temperature. Commercial PPS fibers are produced mainly by meltblown or spunbonded process to give fibers ~20 μm in diameter. In this research, an in-house designed melt electrospinning device was used to fabricate ultrafine PPS fibers, and the e-spinning operation conducted under inert gas to keep PPS fibers from oxidizing. Under the optimum e-spinning conditions (3 mm of nozzle diameter, 30 kV of electrostatic voltage, and 9.5 cm of tip-to-collector distance), the as-spun fibers were less than 8.0 μm in diameter. After characterization, the resultant PPS fibers showed uniform diameter and structural stability. Compared with commercial PPS staple fibers, the obtained fibers had a cold crystallization peak and 10 times higher storage modulus, thereby offering better tensile tenacity and more than 400% elongation at break.