bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Therapy Outcomes When Treating Chronic Kidney Disease Patients with Paricalcitol in German and Austrian Clinical Practice (TOP Study)
Authors: Obermüller Nicholas , Rosenkranz Alexander , Müller Hans-Walter , Hidde Dennis , Veres András , Decker-Burgard Sabine , Weisz Isolde , Geiger Helmut
Published: September 2017

Paricalcitol is approved for prevention and therapy of secondary hyperparathyroidism (sHPT) in patients with chronic kidney disease (CKD), with only short-term data in clinical routine settings. A 12-month observational study was conducted in Germany and Austria (90 centers, 761 patients) from 2008 to 2013. Laboratory values, demographical, and clinical data were documented in 629 dialysis patients and 119 predialysis patients. In predialysis patients, median intact parathormone (iPTH) was 180.0 pg/mL (n = 105) at the start of the study, 115.7 pg/mL (n = 105) at last documentation, and 151.8 pg/mL (n = 50) at month 12, with 32.4% of the last documented iPTH values in the KDOQI (Kidney Disease Outcomes Quality Initiative) target range. In dialysis patients, median iPTH was 425.5 pg/mL (n = 569) at study start, 262.3 pg/mL (n = 569) at last documentation, and 266.1 pg/mL (n = 318) at month 12, with 36.5% of dialysis patients in the KDOQI target range. Intravenous paricalcitol showed more homogenous iPTH control than oral treatment. Combined analysis of all dialysis patients indicated comparable and stable mean serum calcium and phosphate levels throughout the study. Clinical symptoms, such as itching, bone pain, and fatigue, were improved compared with study entry. The spectrum and frequency of adverse events mirrored the known pattern for patients on dialysis. Paricalcitol is efficacious and has a consistent safety profile in sHPT over 12 months.
Metal Substitution Effect on a Three-Dimensional Cyanido-Bridged Fe Spin-Crossover Network
Authors: Imoto Kenta , Takano Shinjiro , Ohkoshi Shin-ichi
Published: September 2017

We report the CoII-substitution effect on a cyanido-bridged three-dimensional FeII spin-crossover network, Fe2[Nb(CN)8](4-pyridinealdoxime)8·2H2O. A series of iron–cobalt octacyanidoniobate, (FexCo1−x)2[Nb(CN)8](4-pyridinealdoxime)8·zH2O, was prepared. In this series, the behavior of FeII spin-crossover changes with the CoII concentration. As the CoII concentration increases, the transition of the spin-crossover becomes gradual and the transition temperature of the spin-crossover shifts towards a lower temperature. Additionally, this series shows magnetic phase transition at a low temperature. In particular, (Fe0.21Co0.79)2[Nb(CN)8](4-pyridinealdoxime)8·zH2O exhibits a Curie temperature of 12 K and a large coercive field of 3100 Oe.
Comparison of Minimal Residual Disease Detection by Multiparameter Flow Cytometry, ASO-qPCR, Droplet Digital PCR, and Deep Sequencing in Patients with Multiple Myeloma Who Underwent Autologous Stem Cell Transplantation
Authors: Takamatsu Hiroyuki
Published: September 2017

Multiple myeloma (MM) is a hematological malignancy with a poor prognosis, characterized by clonal proliferation of plasma cells in the bone marrow (BM). Relapse due to undetected minimal residual disease (MRD) is the leading cause of death among patients with MM. This review summarizes the methods and prognostic value of MRD assessment in BM and autografts from MM patients who underwent autologous stem cell transplantation (ASCT) by multiparameter flow cytometry (MFC), allele-specific oligonucleotide real-time quantitative PCR (ASO-qPCR), droplet digital PCR (ddPCR), and next-generation sequencing (NGS)-based detection methods. MRD assessment using NGS-based approaches has clear prognostic value and better sensitivity compared to traditional methods.
Suitability of EGCG as a Means of Stabilizing a Porcine Osteochondral Xenograft
Authors: Elder Steven , Clune John , Walker Jaylyn , Gloth Paul
Published: September 2017

As a non-crosslinked osteochondral xenograft would be mechanically inferior to native cartilage and vulnerable to premature degradation, we seek a safe and effective method of xenograft stabilization. The purpose of this study was to evaluate the capacity for epigallocatechin gallate (EGCG) to stabilize a decellularized porcine osteochondral xenograft through collagen crosslinking. Our objectives were to assess the effects of EGCG on the degree of crosslinking, mechanical properties, collagenase resistance, cytotoxicity, and in vitro biocompatibility. EGCG is a green tea polyphenol that acts as a collagen crosslinker. Porcine osteochondral plugs were decellularized and then crosslinked by soaking in EGCG. The degree of crosslinking, cartilage compressive stiffness, cartilage-bone interface strength, coefficient of friction, and residual mass after collagenase exposure all increased with an increasing EGCG concentration. With the exception of the coefficient of friction, EGCG treatment could restore mechanical properties to levels equal to, or exceeding those, of native cartilage. EGCG treatment profoundly increased the enzymatic resistance, and 1% EGCG provided protection equivalent to 1% glutaraldehyde. EGCG up to 0.5 mM was essentially not cytotoxic to chondrocytes embedded in alginate, and autologous chondrocytes attached to decellularized, EGCG-fixed cartilage were all viable five days after seeding. Results demonstrate that EGCG has many beneficial effects on a decellularized osteochondral xenograft, and may be suitable for use in stabilizing such a graft prior to implantation for the repair of a defect.
Biodegradable Materials and Metallic Implants—A Review
Authors: Prakasam Mythili , Locs Janis , Salma-Ancane Kristine , Loca Dagnija , Largeteau Alain , Berzina-Cimdina Liga
Published: September 2017

Recent progress made in biomaterials and their clinical applications is well known. In the last five decades, great advances have been made in the field of biomaterials, including ceramics, glasses, polymers, composites, glass-ceramics and metal alloys. A variety of bioimplants are currently used in either one of the aforesaid forms. Some of these materials are designed to degrade or to be resorbed inside the body rather than removing the implant after its function is served. Many properties such as mechanical properties, non-toxicity, surface modification, degradation rate, biocompatibility, and corrosion rate and scaffold design are taken into consideration. The current review focuses on state-of-the-art biodegradable bioceramics, polymers, metal alloys and a few implants that employ bioresorbable/biodegradable materials. The essential functions, properties and their critical factors are discussed in detail, in addition to their challenges to be overcome.
SISI: A New Device for In Situ Incubations at the Ocean Surface
Authors: Rahlff Janina , Stolle Christian , Wurl Oliver
Published: September 2017

The sea-surface microlayer (SML) forms the uppermost boundary layer between atmosphere and ocean, and has distinctive physico-chemical and biological features compared to the underlying water. First findings on metabolic contributions of microorganisms to gas exchange processes across the SML raised the need for new in situ technologies to explore plankton-oxygen turnover in this special habitat. Here, we describe an inexpensive research tool, the Surface In Situ Incubator (SISI), which allows simultaneous incubations of the SML, and water samples from 1 m and 5 m, at the respective depths of origin. The SISI is deployed from a small boat, seaworthy up to 5 bft (Beaufort scale), and due to global positioning system (GPS) tracking, capable of drifting freely for hours or days. We tested the SISI by applying light/dark bottle incubations in the Baltic Sea and the tropical Pacific Ocean under various conditions to present first data on planktonic oxygen turnover rates within the SML, and two subsurface depths. The SISI offers the potential to study plankton-oxygen turnover within the SML under the natural influence of abiotic parameters, and hence, is a valuable tool to routinely monitor their physiological role in biogeochemical cycling and gas exchange processes at, and near, the sea surface.
The Social Investment Capital and the Cargo Volume Transported by Sea: A VAR Approach for Vietnam
Authors: Thi Thuy Hong Nguyen , Thi Lich Hoang , Thanh Nga Bui
Published: September 2017

Social investment capital is one of the factors in Vietnam’s economic growth. It also has a broad impact on many manufacturing and service sectors in the national economy, including maritime transport. This article will apply a quantitative method named vector autoregression (VAR) to define the impacts of social investment capital on the quantity of cargo transported by sea. Special attention will be paid to investment from the government and foreign investors. Recommendations will be suggested to improve the current situation of shipping companies in particular, and the shipping industry in general in Vietnam.
(2-Deoxy-2-{[2-(2-pyridinyl-κN)-4-thiazolecarbonyl-κN3]amino}-α-d-glucopyranose)dichloropalladium(II) Methanol Solvate
Authors: Kodama Shintaro , Nomoto Akihiro , Sakai Yuta , Katao Shouhei , Kakiuchi Kiyomi , Yano Shigenobu , Ogawa Akiya
Published: September 2017

A novel palladium(II) complex with a glycoconjugated 2-(2-pyridyl)thiazole ligand was synthesized. Single-crystal X-ray analysis revealed a packing structure that may be stabilized by hydrogen bonding between sugar moieties and between methanol (crystal solvent) and a sugar moiety.
Interfacial Bonding Energy on the Interface between ZChSnSb/Sn Alloy Layer and Steel Body at Microscale
Authors: Wang Jianmei , Xia Quanzhi , Ma Yang , Meng Fanning , Liang Yinan , Li Zhixiong
Published: September 2017

To investigate the performance of bonding on the interface between ZChSnSb/Sn and steel body, the interfacial bonding energy on the interface of a ZChSnSb/Sn alloy layer and the steel body with or without Sn as an intermediate layer was calculated under the same loadcase using the molecular dynamics simulation software Materials Studio by ACCELRYS, and the interfacial bonding energy under different Babbitt thicknesses was compared. The results show that the bonding energy of the interface with Sn as an intermediate layer is 10% larger than that of the interface without a Sn layer. The interfacial bonding performances of Babbitt and the steel body with Sn as an intermediate layer are better than those of an interface without a Sn layer. When the thickness of the Babbitt layer of bushing is 17.143 Å, the interfacial bonding energy reaches the maximum, and the interfacial bonding performance is optimum. These findings illustrate the bonding mechanism of the interfacial structure from the molecular level so as to ensure the good bonding properties of the interface, which provides a reference for the improvement of the bush manufacturing process from the microscopic point of view.
Synthesis and Charaterization of Silica-Based Aldehyde Chitosan Hybrid Material for Biodiesel Purification
Authors: Da Silva Sandra , De Albuquerque Nilson , De Almeida Rusiene , De Abreu Fabiane
Published: September 2017

This study concerns the development and charaterization of Silica-based aldehyde Chitosan hybrid material as an adsorbent for biodiesel purification. This biocomposite was prepared by sol-gel route and oxidation with periodate, and then characterized. FTIR experiments showed that the hybrid formed presents absorption bands similar to those of Chitosan-Silica, with the exception of the vibrations at 1480 cm−1 and 1570 cm−1 attributed to the symmetrical angular deformation in the N-H plane, and possess large N2 Brunauer–Emmett–Teller (BET) surface areas. Thermogravimetric analysis (TG) and scanning electron microscopy (SEM) was also carried out. Adsorption studies of bioadsorbents involving the analysis of free glycerol, soap, acidity, diglycerides, triglycerides, and fluorescence spectroscopy showed that silica-based aldehyde chitosan has a good affinity for glycerol and a good purification process.
Effect of Protonation State and N-Acetylation of Chitosan on Its Interaction with Xanthan Gum: A Molecular Dynamics Simulation Study
Authors: Dadou Suha , El-Barghouthi Musa , Alabdallah Samer , Badwan Adnan , Antonijevic Milan , Chowdhry Babur
Published: September 2017

Hydrophilic matrices composed of chitosan (CS) and xanthan gum (XG) complexes are of pharmaceutical interest in relation to drug delivery due to their ability to control the release of active ingredients. Molecular dynamics simulations (MDs) have been performed in order to obtain information pertaining to the effect of the state of protonation and degree of N-acetylation (DA) on the molecular conformation of chitosan and its ability to interact with xanthan gum in aqueous solutions. The conformational flexibility of CS was found to be highly dependent on its state of protonation. Upon complexation with XG, a substantial restriction in free rotation around the glycosidic bond was noticed in protonated CS dimers regardless of their DA, whereas deprotonated molecules preserved their free mobility. Calculated values for the free energy of binding between CS and XG revealed the dominant contribution of electrostatic forces on the formation of complexes and that the most stable complexes were formed when CS was at least half-protonated and the DA was ≤50%. The results obtained provide an insight into the main factors governing the interaction between CS and XG, such that they can be manipulated accordingly to produce complexes with the desired controlled-release effect.
Microstructural Evolution of Intermetallic Compound Formed in Boron Steel Hot-Dipped in Al–7%Ni Alloy
Authors: Yun Jung-Gil , Lee Jae-Hyeong , Kwak Sung-Yun , Kang Chung-Yun
Published: September 2017

The microstructural evolution of the intermetallic compound (IMC) layer formed on and in boron steel that was hot dipped in an Al–7Ni (wt %) bath at 690 °C for 30–180 s was investigated, and the growth mechanism of the IMC was identified. Except for the solidification structure of Al, the reaction layer consisted of one layer on the steel surface and two layers in the steel interior. The reaction phase formed on the original surface of the steel was the Al9FeNi (T) phase, which has a monoclinic (space group: P21/c) crystal structure. The reaction phase formed from the T phase was the Fe2Al5 (η) phase, which is orthorhombic (space group: Cmcm). The variation in thickness of the η phase increased linearly with increasing dipping time, which is in accordance with the diffusion growth, a growth mechanism of the η phase in Al-coated pure Fe and low-carbon steels. The Fe3AlC (κ) phase (which had a band shape with a width of 100 nm) and a cubic system were formed along the interface between the Fe2Al5 (η) phase and the steel.
The Effects of Incorporated Sn in Resynthesized Ni-Rich Cathode Materials on Their Lithium-Ion Battery Performance
Authors: Kang Ga-hee , Lee Ko-woon , Kwon Kyungjung , Song Junho
Published: September 2017

LiNixCoyMnz (NCM), one of the most promising candidates for high-capacity cathode materials in Li-ion batteries (LIBs), is synthesized with various amounts of Sn. Sn-incorporated NCM from the resynthesis of NMC in leach liquor containing Sn from spent LIBs is characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, particle strength tests, and electrochemical tests. Sn-incorporated NCM has a globular form, and the uniform distribution of Sn inside cathode materials is confirmed. As Sn is introduced, the (003) diffraction peak tends to shift to a smaller angle and particle breaking strength increases. It is found that Sn-incorporated cathode active materials have better cycle performance and rate capability than pristine cathode active material although the discharge capacity slightly decreases. Because there is a trade-off between decreased discharge capacity and improved cycling and rate performance, the incorporation of Sn in resynthesized NCM should be carefully designed and conducted.
Modelling and Experimental Verification of Step Response Overshoot Removal in Electrothermally-Actuated MEMS Mirrors
Authors: Li Mengyuan , Chen Qiao , Liu Yabing , Ding Yingtao , Xie Huikai
Published: September 2017

Micro-electro-mechanical system (MEMS) mirrors are widely used for optical modulation, attenuation, steering, switching and tracking. In most cases, MEMS mirrors are packaged in air, resulting in overshoot and ringing upon actuation. In this paper, an electrothermal bimorph MEMS mirror that does not generate overshoot in step response, even operating in air, is reported. This is achieved by properly designing the thermal response time and the mechanical resonance without using any open-loop or closed-loop control. Electrothermal and thermomechanical lumped-element models are established. According to the analysis, when setting the product of the thermal response time and the fundamental resonance frequency to be greater than Q/2π, the mechanical overshoot and oscillation caused by a step signal can be eliminated effectively. This method is verified experimentally with fabricated electrothermal bimorph MEMS mirrors.
Comparison of Three Key Marine Shale Reservoirs in the Southeastern Margin of the Sichuan Basin, SW China
Authors: Liu Jun , Yao Yanbin , Liu Dameng , Pan Zhejun , Cai Yidong
Published: September 2017

This study performs a comprehensive comparison of three key marine shale reservoirs in the southeastern margin of the Sichuan Basin, and explains why commercial gas production was only achieved in the Lower Silurian Longmaxi (LSL) and Upper Ordovician Wufeng (UOW) formations, but not in the Lower Cambrian Niutitang (LCN) formation. The experimental methods included in situ gas content and gas composition tests, methane adsorption analysis, low-pressure N2 adsorption, field emission scanning electron microscopy (FE-SEM), and total organic carbon (TOC) and vitrinite reflectance (Ro) analyses to evaluate the lithology, mineralogy, physical properties of the reservoir, organic geochemistry, in situ gas content and methane adsorption capacity characteristics of the three shales. The LCN shale has lower quartz and clay mineral contents and a low brittleness index, but higher contents of feldspar, pyrite and carbonate minerals than the LSL and UOW shales. The porosity and permeability of the LSL and UOW shales are higher than those of the LCN shale. The primary contributions to the high permeability in the LSL shale are its well-developed fractures and organic matter pores. In contrast, the over-mature LCN shale is unfavorable for the development of organic pores and fractures. Although the LCN shale has a higher methane sorption capacity than the LSL and UOW shales, the gas content and methane saturation of the LCN shale are distinctly lower than those of the LSL and UOW shales. This is primarily due to gas migration from the LCN shale, resulting from the activities of tectonic uplift and the unconformable contact between the LCN shale and the Dengying formation. When compared with gas shale in North America, the LSL shale is the most favorable shale reservoir out of the three Sichuan shales, while the combination of the LSL and UOW shales is also potentially productive. However, the individual single layer production of the UOW or LCN shales is still limited due to poor resource potential and/or reservoir physical characteristics in the study area.
Immobilization of Moniliella spathulata R25L270 Lipase on Ionic, Hydrophobic and Covalent Supports: Functional Properties and Hydrolysis of Sardine Oil
Authors: Souza Lívia , Moreno-Perez Sonia , Fernández Lorente Gloria , Cipolatti Eliane , De Oliveira Débora , Resende Rodrigo , Pessela Benevides
Published: September 2017

The oleaginous yeast Moniliella spathulata R25L270 was the first yeast able to grow and produce extracellular lipase using Macaúba (Acrocomia aculeate) cake as substrate. The novel lipase was recently identified, and presented promising features for biotechnological applications. The M. spathulata R25L270 lipase efficiently hydrolyzed vegetable and animal oils, and showed selectivity for generating cis-5,8,11,15,17-eicosapentaenoic acid from sardine oil. The enzyme can act in a wide range of temperatures (25–48 °C) and pH (6.5–8.4). The present study deals with the immobilization of M. spathulata R25L270 lipase on hydrophobic, covalent and ionic supports to select the most active biocatalyst capable to obtain omega-3 fatty acids (PUFA) from sardine oil. Nine immobilized agarose derivatives were prepared and biochemically characterized for thermostability, pH stability and catalytic properties (KM and Vmax). Ionic supports improved the enzyme–substrate affinity; however, it was not an effective strategy to increase the M. spathulata R25L270 lipase stability against pH and temperature. Covalent support resulted in a biocatalyst with decreased activity, but high thermostability. The enzyme was most stabilized when immobilized on hydrophobic supports, especially Octyl-Sepharose. Compared with the free enzyme, the half-life of the Octyl-Sepharose derivative at 60 °C increased 10-fold, and lipase stability under acidic conditions was achieved. The Octyl-Sepharose derivative was selected to obtain omega-3 fatty acids from sardine oil, and the maximal enzyme selectivity was achieved at pH 5.0.
Biomimetic-Functionalized, Tannic Acid-Templated Mesoporous Silica as a New Support for Immobilization of NHase
Authors: Gao Jun-kai , Zhang Zi-jun , Jiang Yan-jun , Chen Yan , Gao Shu-feng
Published: September 2017

Tannic acid-templated mesoporous silica (TAMS) was synthesized using a simple nonsurfactant template method and dopamine-functionalized TAMS (Dop-TAMS), which was prepared via a biomimetic coating, was developed as a new support for immobilization of NHase (NHase@Dop-TAMS). The Dop-TAMS was thoroughly characterized by the transmission electron microscopy (TEM), scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET), and Fourier transform infrared (FT-IR) and the results showed that the Dop-TAMS possessed sufficiently large pore size and volume for the accommodation of NHase. Studying the thermal stability, storage, shaking stability, and pH stability of the free and immobilized NHase indicated that the catalytic properties of NHase@Dop-TAMS were significantly enhanced. Moreover, the NHase@Dop-TAMS exhibited good reusability. All the results demonstrated that Dop-TAMS could be used as an excellent matrix for the immobilization of NHase.
Glycyrrhetinic Acid Liposomes Containing Mannose-Diester Lauric Diacid-Cholesterol Conjugate Synthesized by Lipase-Catalytic Acylation for Liver-Specific Delivery
Authors: Chen Jing , Chen Yuchao , Cheng Yi , Gao Youheng
Published: September 2017

Mannose-diester lauric diacid-cholesterol (Man-DLD-Chol), as a liposomal target ligand, was synthesized by lipase catalyzed in a non-aqueous medium. Its chemical structure was confirmed by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Glycyrrhetinic acid (GA) liposomes containing Man-DLD-Chol (Man-DLD-Chol-GA-Lp) were prepared by the film-dispersion method. We evaluated the characterizations of liposomes, drug-release in vitro, the hemolytic test, cellular uptake, pharmacokinetics, and the tissue distributions. The cellular uptake in vitro suggested that the uptake of Man-DLD-Chol-modified liposomes was significantly higher than that of unmodified liposomes in HepG2 cells. Pharmacokinetic parameters indicated that Man-DLD-Chol-GA-Lp was eliminated more rapidly than GA-Lp. In tissue distributions, the targeting efficiency (Te) of Man-DLD-Chol-GA-Lp on liver was 54.67%, relative targeting efficiency (RTe) was 3.39, relative uptake rate (Re) was 4.78, and peak concentration ratio (Ce) was 3.46. All these results supported the hypothesis that Man-DLD-Chol would be an efficient liposomal carrier, and demonstrated that Man-DLD-Chol-GA-Lp has potential as a drug delivery for liver-targeting therapy.
Kinetics and Molecular Docking Studies of 6-Formyl Umbelliferone Isolated from Angelica decursiva as an Inhibitor of Cholinesterase and BACE1
Authors: Ali Md , Seong Su , Reddy Machireddy , Seo Sung , Choi Jae , Jung Hyun
Published: September 2017

Coumarins, which have low toxicity, are present in some natural foods, and are used in various herbal remedies, have attracted interest in recent years because of their potential medicinal properties. In this study, we report the isolation of two natural coumarins, namely umbelliferone (1) and 6-formyl umbelliferone (2), from Angelica decursiva, and the synthesis of 8-formyl umbelliferone (3) from 1. We investigated the anti-Alzheimer disease (anti-AD) potential of these coumarins by assessing their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1). Among these coumarins, 2 exhibited poor inhibitory activity against AChE and BChE, and modest activity against BACE1. Structure–activity relationship analysis showed that 2 has an aldehyde group at the C-6 position, and exhibited strong anti-AD activity, whereas the presence or absence of an aldehyde group at the C-8 position reduced the anti-AD activity of 3 and 1, respectively. In addition, 2 exhibited concentration-dependent inhibition of peroxynitrite-mediated protein tyrosine nitration. A kinetic study revealed that 2 and 3 non-competitively inhibited BACE1. To confirm enzyme inhibition, we predicted the 3D structures of AChE and BACE1, and used AutoDock 4.2 to simulate binding of coumarins to these enzymes. The blind docking studies demonstrated that these molecules could interact with both the catalytic active sites and peripheral anionic sites of AChE and BACE1. Together, our results indicate that 2 has an interesting inhibitory activity in vitro, and can be used in further studies to develop therapeutic modalities for the treatment of AD.
Discriminative Analysis of Different Grades of Gaharu (Aquilaria malaccensis Lamk.) via 1H-NMR-Based Metabolomics Using PLS-DA and Random Forests Classification Models
Authors: Ismail Siti , Maulidiani M. , Akhtar Muhammad , Abas Faridah , Ismail Intan , Khatib Alfi , Ali Nor , Shaari Khozirah
Published: September 2017

Gaharu (agarwood, Aquilaria malaccensis Lamk.) is a valuable tropical rainforest product traded internationally for its distinctive fragrance. It is not only popular as incense and in perfumery, but also favored in traditional medicine due to its sedative, carminative, cardioprotective and analgesic effects. The current study addresses the chemical differences and similarities between gaharu samples of different grades, obtained commercially, using 1H-NMR-based metabolomics. Two classification models: partial least squares-discriminant analysis (PLS-DA) and Random Forests were developed to classify the gaharu samples on the basis of their chemical constituents. The gaharu samples could be reclassified into a ‘high grade’ group (samples A, B and D), characterized by high contents of kusunol, jinkohol, and 10-epi-γ-eudesmol; an ‘intermediate grade’ group (samples C, F and G), dominated by fatty acid and vanillic acid; and a ‘low grade’ group (sample E and H), which had higher contents of aquilarone derivatives and phenylethyl chromones. The results showed that 1H- NMR-based metabolomics can be a potential method to grade the quality of gaharu samples on the basis of their chemical constituents.
Pharmacokinetics, Tissue Distribution, and Elimination of Three Active Alkaloids in Rats after Oral Administration of the Effective Fraction of Alkaloids from Ramulus Mori, an Innovative Hypoglycemic Agent
Authors: Yang Shuang , Mi Jiaqi , Liu Zhihao , Wang Baolian , Xia Xuejun , Wang Renyun , Liu Yuling , Li Yan
Published: September 2017

In this study, we systematically investigated the plasma pharmacokinetics, tissue distribution, and elimination of three active alkaloids after oral administration of the effective fraction of alkaloids from Ramulus Mori (SZ–A)—an innovative hypoglycemic agent—in rats. Moreover, the influences of other components in SZ–A on dynamic process of alkaloids were explored for the first time. The results showed that 1-deoxynojirimycin (DNJ), fagomine (FGM) and 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) exhibited nonlinear pharmacokinetics following oral administration of SZ–A (40–1000 mg/kg). The prolonged t1/2 and greater area under concentration-time curve (AUC) versus time (AUC0–t) of DNJ for SZ–A than for purified DNJ has been observed after both oral and intravenous administration. It was found that other components in SZ–A could enhance the absorption of DNJ through the intestinal barrier. The major distribution tissues of DNJ, FGM, and DAB were the gastrointestinal tract, liver, and kidney. Three alkaloids were mainly excreted into urine and feces, but less into bile. Interestingly, the excess excretion of FGM was revealed to be partly due to the biotransformation of other components in SZ–A via gut microbiota. These information provide a rational basis for the use of SZ–A in clinical practice.
Stealth Biocompatible Si-Based Nanoparticles for Biomedical Applications
Authors: Liu Wei , Chaix Arnaud , Gary-Bobo Magali , Angeletti Bernard , Masion Armand , Da Silva Afitz , Daurat Morgane , Lichon Laure , Garcia Marcel , Morère Alain , El Cheikh Khaled , Durand Jean-Olivier , Cunin Frédérique , Auffan Mélanie
Published: September 2017

A challenge regarding the design of nanocarriers for drug delivery is to prevent their recognition by the immune system. To improve the blood residence time and prevent their capture by organs, nanoparticles can be designed with stealth properties using polymeric coating. In this study, we focused on the influence of surface modification with polyethylene glycol and/or mannose on the stealth behavior of porous silicon nanoparticles (pSiNP, ~200 nm). In vivo biodistribution of pSiNPs formulations were evaluated in mice 5 h after intravenous injection. Results indicated that the distribution in the organs was surface functionalization-dependent. Pristine pSiNPs and PEGylated pSiNPs were distributed mainly in the liver and spleen, while mannose-functionalized pSiNPs escaped capture by the spleen, and had higher blood retention. The most efficient stealth behavior was observed with PEGylated pSiNPs anchored with mannose that were the most excreted in urine at 5 h. The biodegradation kinetics evaluated in vitro were in agreement with these in vivo observations. The biocompatibility of the pristine and functionalized pSiNPs was confirmed in vitro on human cell lines and in vivo by cytotoxic and systemic inflammation investigations, respectively. With their biocompatibility, biodegradability, and stealth properties, the pSiNPs functionalized with mannose and PEG show promising potential for biomedical applications.
Practical Liposomal Formulation for Taxanes with Polyethoxylated Castor Oil and Ethanol with Complete Encapsulation Efficiency and High Loading Efficiency
Authors: Shigehiro Tsukasa , Masuda Junko , Saito Shoki , Khayrani Apriliana , Jinno Kazumasa , Seno Akimasa , Vaidyanath Arun , Mizutani Akifumi , Kasai Tomonari , Murakami Hiroshi , Satoh Ayano , Ito Tetsuya , Hamada Hiroki , Seno Yuhki , Mandai Tadakatsu , Seno Masaharu
Published: September 2017

Taxanes including paclitaxel and docetaxel are effective anticancer agents preferably sufficient for liposomal drug delivery. However, the encapsulation of these drugs with effective amounts into conventional liposomes is difficult due to their high hydrophobicity. Therefore, an effective encapsulation strategy for liposomal taxanes has been eagerly anticipated. In this study, the mixture of polyethoxylated castor oil (Cremophor EL) and ethanol containing phosphate buffered saline termed as CEP was employed as a solvent of the inner hydrophilic core of liposomes where taxanes should be incorporated. Docetaxel-, paclitaxel-, or 7-oxacetylglycosylated paclitaxel-encapsulating liposomes were successfully prepared with almost 100% of encapsulation efficiency and 29.9, 15.4, or 29.1 mol% of loading efficiency, respectively. We then applied the docetaxel-encapsulating liposomes for targeted drug delivery. Docetaxel-encapsulating liposomes were successfully developed HER2-targeted drug delivery by coupling HER2-specific binding peptide on liposome surface. The HER2-targeting liposomes exhibited HER2-specific internalization and enhanced anticancer activity in vitro. Therefore, we propose the sophisticated preparation of liposomal taxanes using CEP as a promising formulation for effective cancer therapies.
Prospective Study of Nut Consumption and Incidence of Metabolic Syndrome: Tehran Lipid and Glucose Study
Authors: Hosseinpour-Niazi Somayeh , Hosseini Shabnam , Mirmiran Parvin , Azizi Fereidoun
Published: September 2017

This study aimed to assess the association of various types of nut per se, and total nut consumption with the incidence of metabolic syndrome (MetS). A 6.2 ± 0.7-year population-based prospective study was conducted among 1265 adults, aged 19–74 years, participants of the Tehran Lipid and Glucose Study. A 168-item semi-quantitative food frequency questionnaire was used to collect information on nut consumption. MetS was defined according to the Joint Interim Statement guidelines and 276 new cases of MetS were identified. Median ± interquartile range of nut consumption was 2.08 (0.88–5.68) servings/week. After adjusting for family history of diabetes, age, gender, smoking, physical activity, fasting serum glucose at baseline, serum high density lipoprotein cholesterol (HDL-C) at baseline, energy intake, fiber, macronutrients, cholesterol intake, fruit, vegetables, dairy products and body mass index (BMI), a statistically significant decrease was observed in MetS in the third (≥5 servings/week) tertile of nuts (odds ratio: 0.68, 95% CI: 0.44–0.91, p trend: 0.03) compared with the lowest (≤1 serving/week). Walnut consumption showed a significant, inverse association with MetS risk; associations for other nut varieties were not significant. For each additional serving/week of walnuts consumed, incidence of MetS decreased by 3% (ORs: 0.97 CI: 0.93–0.99), after adjusting for confounding factors. Total nut consumption, especially walnuts, reduces the risk of MetS.
Coptidis Rhizoma Prevents Heat Stress-Induced Brain Damage and Cognitive Impairment in Mice
Authors: Moon Minho , Huh Eugene , Lee Wonil , Song Eun , Hwang Deok-Sang , Lee Tae , Oh Myung
Published: September 2017

Heat stress conditions lead to neuroinflammation, neuronal death, and memory loss in animals. Coptidis Rhizoma (CR) exhibits potent fever-reducing effects and has been used as an important traditional medicinal herb for treating fever. However, to date, the effects of antipyretic CR on heat-induced brain damages have not been investigated. In this study, CR significantly reduced the elevation of ear and rectal temperatures after exposure to heat in mice. Additionally, CR attenuated hyperthermia-induced stress responses, such as release of cortisol into the blood, and upregulation of heat shock protein and c-Fos in the hypothalamus and hippocampus of mice. The administration of CR inhibited gliosis and neuronal loss induced by thermal stress in the hippocampal CA3 region. Treatment with CR also reduced the heat stress-induced expression of nuclear factor kappa β, tumor necrosis factor-α, and interleukin-1β (IL-1β) in the hippocampus. Moreover, CR significantly decreased proinflammatory mediators such as IL-9 and IL-13 in the heat-stressed hypothalamus. Furthermore, CR attenuated cognitive dysfunction triggered by thermal stress. These results indicate that CR protects the brain against heat stress-mediated brain damage via amelioration of hyperthermia and neuroinflammation in mice, suggesting that fever-reducing CR can attenuate thermal stress-induced neuropathology.
Therapeutic Effects of Olive and Its Derivatives on Osteoarthritis: From Bench to Bedside
Authors: Chin Kok-Yong , Pang Kok-Lun
Published: September 2017

Osteoarthritis is a major cause of morbidity among the elderly worldwide. It is a disease characterized by localized inflammation of the joint and destruction of cartilage, leading to loss of function. Impaired chondrocyte repair mechanisms, due to inflammation, oxidative stress and autophagy, play important roles in the pathogenesis of osteoarthritis. Olive and its derivatives, which possess anti-inflammatory, antioxidant and autophagy-enhancing activities, are suitable candidates for therapeutic interventions for osteoarthritis. This review aimed to summarize the current evidence on the effects of olive and its derivatives, on osteoarthritis and chondrocytes. The literature on animal and human studies has demonstrated a beneficial effect of olive and its derivatives on the progression of osteoarthritis. In vitro studies have suggested that the augmentation of autophagy (though sirtuin-1) and suppression of inflammation by olive polyphenols could contribute to the chondroprotective effects of olive polyphenols. More research and well-planned clinical trials are required to justify the use of olive-based treatment in osteoarthritis.
Beneficial Effects of Small Molecule Oligopeptides Isolated from Panax ginseng Meyer on Pancreatic Beta-Cell Dysfunction and Death in Diabetic Rats
Authors: Xu Meihong , Sun Bin , Li Di , Mao Ruixue , Li Hui , Li Yong , Wang Junbo
Published: September 2017

To determine whether treatment with ginseng oligopeptides (GOPs) could modulate hyperglycemia related to type 2 diabetes mellitus (T2DM) in rats induced by high-fat diet and low doses of alloxan, type 2 diabetes was induced in male Sprague–Dawley (SD) rats by injecting them once with 105 mg/kg alloxan and feeding them high-carbohydrate/high-fat diet with or without GOP administration (0.125, 0.5, and 2.0 g/kg Body Weight) for 7, 24, and 52 weeks. Oral glucose test tolerance (OGTT), plasma glucose, serum insulin, level of antioxidant, and beta cell function were measured. Morphological observation and immunohistochemistry study of insulin of islets was performed by light microscopy. The insulin level and the expression of NF-κB and Bcl-2 family in pancreatic islets were also detected by Western blot analysis. In addition, survival time and survival rate were observed. After the treatment, the abnormal OGTT were partially reversed by GOPs treatment in diabetic rats. The efficacy of GOPs was manifested in the amelioration of pancreatic damage, as determined by microscopy analysis. Moreover, GOPs treatment increased the normal insulin content and decreased the expression of the NF-κB-signaling pathway. Compared with those in the control model, the survival time and rate were significantly longer. It is suggested that GOPs exhibit auxiliary therapeutic potential for diabetes.
Ferulic Acid Promotes Hypertrophic Growth of Fast Skeletal Muscle in Zebrafish Model
Authors: Wen Ya , Ushio Hideki
Published: September 2017

As a widely distributed and natural existing antioxidant, ferulic acid and its functions have been extensively studied in recent decades. In the present study, hypertrophic growth of fast skeletal myofibers was observed in adult zebrafish after ferulic acid administration for 30 days, being reflected in increased body weight, body mass index (BMI), and muscle mass, along with an enlarged cross-sectional area of myofibers. qRT-PCR analyses demonstrated the up-regulation of relative mRNA expression levels of myogenic transcriptional factors (MyoD, myogenin and serum response factor (SRF)) and their target genes encoding sarcomeric unit proteins involved in muscular hypertrophy (skeletal alpha-actin, myosin heavy chain, tropomyosin, and troponin I). Western blot analyses detected a higher phosphorylated level of zTOR (zebrafish target of rapamycin), p70S6K, and 4E-BP1, which suggests an enhanced translation efficiency and protein synthesis capacity of fast skeletal muscle myofibers. These changes in transcription and translation finally converge and lead to higher protein contents in myofibers, as confirmed by elevated levels of myosin heavy chain (MyHC), and an increased muscle mass. To the best of our knowledge, these findings have been reported for the first time in vivo and suggest potential applications of ferulic acid as functional food additives and dietary supplements owing to its ability to promote muscle growth.
Nanotechnologies in Pancreatic Cancer Therapy
Authors: Manzur Ayesha , Oluwasanmi Adeolu , Moss Darren , Curtis Anthony , Hoskins Clare
Published: September 2017

Pancreatic cancer has been classified as a cancer of unmet need. After diagnosis the patient prognosis is dismal with few surviving over 5 years. Treatment regimes are highly patient variable and often the patients are too sick to undergo surgical resection or chemotherapy. These chemotherapies are not effective often because patients are diagnosed at late stages and tumour metastasis has occurred. Nanotechnology can be used in order to formulate potent anticancer agents to improve their physicochemical properties such as poor aqueous solubility or prolong circulation times after administration resulting in improved efficacy. Studies have reported the use of nanotechnologies to improve the efficacy of gemcitabine (the current first line treatment) as well as investigating the potential of using other drug molecules which have previously shown promise but were unable to be utilised due to the inability to administer through appropriate routes—often related to solubility. Of the nanotechnologies reported, many can offer site specific targeting to the site of action as well as a plethora of other multifunctional properties such as image guidance and controlled release. This review focuses on the use of the major nanotechnologies both under pre-clinical development and those which have recently been approved for use in pancreatic cancer therapy.
Fabrication of Hypericin Imprinted Polymer Nanospheres via Thiol-Yne Click Reaction
Authors: Pei Yuxin , Fan Fengfeng , Wang Xinxin , Feng Weiwei , Hou Yong , Pei Zhichao
Published: September 2017

To fabricate molecularly imprinted polymer nanospheres via click reaction, five different clickable compounds were synthesized and two types of click reactions (azide-alkyne and thiol-yne) were explored. It was found that molecularly imprinted polymer nanospheres could be successfully synthesized via thiol-yne click reaction using 3,5-diethynyl-pyridine (1) as the monomer, tris(3-mercaptopropionate) (tri-thiol, 5) as the crosslinker, and hypericin as the template (MIP–NSHs). The click polymerization completed in merely 4 h to produce the desired MIP–NSHs, which were characterized by FTIR, SEM, DLS, and BET, respectively. The reaction conditions for adsorption capacity and selectivity towards hypericin were optimized, and the MIP–NSHs synthesized under the optimized conditions showed a high adsorption capacity (Q = 6.03 μmol•g−1) towards hypericin. The imprinting factors of MIP–NSHs towards hypericin, protohypericin, and emodin were 2.44, 2.88, and 2.10, respectively.
Reframing Catholic Theological Ethics: Summary and Application
Authors: Selling Joseph
Published: September 2017

This text represents a summary of the major points developed in the book, Reframing Catholic Theological Ethics, and a brief overview of how the author understands the relation between religion, ethics, and the building of a virtuous community. The main points of the book involve the anatomy of “the moral event” that includes a breakdown of all the elements necessary to consider before one arrives at ethical judgments and decision-making. Foundations are brought forth for these elements, each of which exhibits its own characteristics. The good and evil details of actions and circumstances that make up behavior are based upon an analysis of what is beneficial or harmful to human persons, integrally and adequately considered. Behaviors themselves are considered right or wrong in relation to whether they are appropriate ways of achieving one’s intended ends. Then, the distinction between good and bad is related to one’s virtuous or vicious dispositions, which necessitates a revised understanding of virtue. Based upon a view of religion that provides a formulation of principles that guide the life of the believing community, it is suggested that these principles encourage a commitment to ends or goals that serve the maintenance and advance of a community’s ethics.
Special Issue “International Conference of Spirituality in Healthcare. Nurturing the Spirit”—Trinity College Dublin 2016
Authors: Timmins Fiona , Egan Richard , Flanagan Bernadette , Muldowney Yvonne , OBoyle Colm , Brady Vivienne , Whelan Jacqueline , Neenan Kathleen , McSherry Wilfred
Published: September 2017

This is an editorial of a Special Issue regarding the International Conference of Spirituality in Healthcare held in the School of Nursing and Midwifery, Trinity College Dublin, Republic of Ireland (ROI), on June 2016 (Spirituality Research and Innovation Group 2016).[...]
Tsipporah, Her Son, and the Bridegroom of Blood: Attending to the Bodies in Ex 4:24–26
Authors: Murray Talbot Margaret
Published: September 2017

Through the centuries, scholars and readers have looked through a variety of lenses to discover what might be revealed by the story of Tsipporah’s circumcision of her son in Exodus 4, and to assign meanings to it. The ambiguity of the language and the particular interests of readers in their contexts allow for a breadth of possibilities. However, in most cases, the son and his body fail to attract much scholarly concern. In this reading, I suggest that considering more intently the bodies of the son, Tsipporah, and the deity through the lens of affect theory offers a fresh understanding of Tsipporah’s utterance following the cutting of her son’s foreskin. Teresa Brennan’s work on the transmission of affect breaks down the “foundational fallacy” of the individuated bodies of the three, allowing the deity’s threat, the son’s pain, and the mother’s response to affect the way Tsipporah’s words might be heard and understood.
Virtual Pilgrimage and Virtual Geography: Power of Liao Miniature Pagodas (907-1125)
Authors: Kim Youn-mi
Published: September 2017

This paper examines the role of the miniature in Buddhist ritual, through analyses of miniature pagodas from middle-period China. Due to the otherworldly sensations they evoked and their theatrical nature, miniatures were often endowed with magical and performative power in funerary and religious contexts. The miniature pagodas from the Liao empire (907–1125) were replicas of the stupa monuments (the prototype of the pagoda) at the Eight Great Sacred Places in India. Adopting ritual theories and a comparative approach, this paper illuminates how the Liao miniature pagodas were devised to symbolically transfer the sacred places to the Liao empire in northeast China, allowing Liao Buddhists to make a virtual pilgrimage to the Buddha’s homeland by circumambulating the pagoda. The ways in which they functioned in the Buddhist ritual were similar to the small-scale copies of the Holy Sepulcher in medieval Europe. Their power—contrary to common sense—originated from their miniature size and intentional rejection of their sacred prototype. Through these miniatures, the banal ritual of pagoda circumambulation was transformed into an imaginary journey to the distant holy land, which was believed to be more efficacious and meritorious than an actual pilgrimage, and the prairie of northeast China was turned into the most sacred place in the Buddhist world.