bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise Training Impacts Cardiac Mitochondrial Proteome Remodeling in Murine Urothelial Carcinoma
Authors: Ferreira Rita , Neuparth Maria João , Nogueira-Ferreira Rita , Magalhães Sandra , Aroso Miguel , Bovolini José António , Lara Santos Lúcio , Oliveira Paula , Vitorino Rui , Moreira-Gonçalves Daniel
Published: December 2018

Cardiac dysfunction secondary to cancer may exert a negative impact in patients’ tolerance to therapeutics, quality of life, and survival. The aim of this study was to evaluate the potential therapeutic effect of exercise training on the heart in the setting of cancer, after diagnosis. Thus, the molecular pathways harbored in heart mitochondria from a murine model of chemically-induced urothelial carcinoma submitted to 8-weeks of high intensity treadmill exercise were characterized using mass spectrometry-based proteomics. Data highlight the protective effects of high intensity exercise training in preventing left ventricle diastolic dysfunction, fibrosis, and structural derangement observed in tumor-bearing mice. At the mitochondrial level, exercise training counteracted the lower ability to produce ATP observed in the heart of animals with urothelial carcinoma and induced the up-regulation of fatty acid oxidation and down-regulation of the biological process “cardiac morphogenesis”. Taken together, our data support the prescription of exercise training after cancer diagnosis for the management of disease-related cardiac dysfunction.
Transformer Coupling and Its Modelling for the Flux-Ramp Modulation of rf-SQUIDs
Authors: Carniti Paolo , Cassina Lorenzo , Faverzani Marco , Ferri Elena , Giachero Andrea , Gotti Claudio , Maino Matteo , Nucciotti Angelo , Pessina Gianluigi , Puiu Andrei
Published: December 2018

Microwave SQUID (Superconducting QUantum Interference Device) multiplexing is a suitable technique for reading a large number of detector channels, using only a few connecting lines. In the HOLMESexperiment, this is based on inductively coupled rf-SQUIDs fed by TES (Transition Edge Sensors). Operation of the whole rf-SQUID chain is achieved with a single transmission line, by means of the recently introduced flux-ramp modulation technique—a sawtooth signal which allows signal reconstruction while operating the rf-SQUIDs in an open loop condition. Due to the crucial role of the sawtooth signal, it is very important that it does not suffer from ground-loop disturbances and electromagnetic interference (EMI). Introducing a transformer between the sawtooth source and the SQUID is very effective in suppressing disturbances. The sawtooth signal has both slow and fast components, and the frequency can vary between a few kHz up to a MHz, depending on the TES signal and SQUID characteristics. A transformer able to handle such a broad range of conditions must have very stringent characteristics and needs to be custom designed. Our solution exploits standard commercial and inexpensive transformers for LAN networks, stacked in a user-selectable number, to better fit the bandwidth requirements. A model that allows handling of the low- and high-frequency operating range has been developed.
Influence of Traditional Cardiovascular Risk Factors on Carotid and Femoral Atherosclerotic Plaque Volume as Measured by Three-Dimensional Ultrasound
Authors: Noflatscher Maria , Schreinlechner Michael , Sommer Philip , Kerschbaum Julia , Berggren Katharina , Theurl Markus , Kirchmair Rudolf , Marschang Peter
Published: December 2018

Background: Atherosclerosis is a systemic multifocal disease with a preference for the branching points of the arteries. In this study, we quantitatively measured carotid and femoral plaque volume in subjects with cardiovascular risk factors (CVRF) and/or established atherosclerotic disease using a 3D ultrasound technique. Methods: In this prospective, single-centre study, we included 404 patients (median age 64; 56.9% men) with at least one CVRF or established cardiovascular disease. Plaque volume was measured using 3D ultrasound equipped with an automated software. Results: We found a strong correlation of plaque volume with CVRF and the number of vascular beds involved. The strongest associations with total and femoral plaque volume were noted for smoking, hypertension, age, as well as for the presence of peripheral arterial occlusive disease (p < 0.05). Carotid plaque volume was best predicted by hyperlipidaemia, hypertension, age, as well as the presence of cerebrovascular disease and coronary artery disease (p < 0.05). Conclusion: We conclude that smoking appears to be associated with total and femoral plaque volume, whereas hyperlipidaemia seems to be associated with carotid plaque volume. Measurement of 3D plaque volume is a practical and reproducible technique with the potential to become an additional screening tool in cardiovascular risk stratification.
Multi-Modal Medical Image Registration with Full or Partial Data: A Manifold Learning Approach
Authors: Bashiri Fereshteh S. , Baghaie Ahmadreza , Rostami Reihaneh , Yu Zeyun , D’Souza Roshan M.
Published: December 2018

Multi-modal image registration is the primary step in integrating information stored in two or more images, which are captured using multiple imaging modalities. In addition to intensity variations and structural differences between images, they may have partial or full overlap, which adds an extra hurdle to the success of registration process. In this contribution, we propose a multi-modal to mono-modal transformation method that facilitates direct application of well-founded mono-modal registration methods in order to obtain accurate alignment of multi-modal images in both cases, with complete (full) and incomplete (partial) overlap. The proposed transformation facilitates recovering strong scales, rotations, and translations. We explain the method thoroughly and discuss the choice of parameters. For evaluation purposes, the effectiveness of the proposed method is examined and compared with widely used information theory-based techniques using simulated and clinical human brain images with full data. Using RIRE dataset, mean absolute error of 1.37, 1.00, and 1.41 mm are obtained for registering CT images with PD-, T1-, and T2-MRIs, respectively. In the end, we empirically investigate the efficacy of the proposed transformation in registering multi-modal partially overlapped images.
A Communication Theoretic Interpretation of Modern Portfolio Theory Including Short Sales, Leverage and Transaction Costs
Authors: Arici Giorgio , Dalai Marco , Leonardi Riccardo , Spalvieri Arnaldo
Published: December 2018

Modern Portfolio Theory is the ground upon which most works in portfolio optimization context find their foundations. Many studies attempt to extend the Modern Portfolio Theory to include short sale, leverage and transaction costs, features not considered in Markowitz’s seminal work from 1952. The drawback of such theories is that they complicate considerably the simplicity of the original technique. Here, we propose a simple and unified method, which takes inspiration from, and shows connections with the matched filter theory in communications, to evaluate the best portfolio allocation with the possibility of including a leverage factor and short sales. Finally, we extend the presented method to also consider the transaction costs.
Grain-Size Distribution Effects on the Attenuation of Laser-Generated Ultrasound in α-Titanium Alloy
Authors: Bai Xue , Zhao Yang , Ma Jian , Liu Yunxi , Wang Qiwu
Published: December 2018

Average grain size is usually used to describe a polycrystalline medium; however, many investigations demonstrate the grain-size distribution has a measurable effect on most of mechanical properties. This paper addresses the experimental quantification for the effects of grain-size distribution on attenuation in α-titanium alloy by laser ultrasonics. Microstructures with different mean grain sizes of 26–49 μm are obtained via annealing at 800 °C for different holding times, having an approximately log-normal distribution of grain sizes. Experimental measurements were examined by using two different theoretical models: (i) the classical Rokhlin’s model considering a single mean grain size, and (ii) the improved Turner’s model incorporating a log-normal distribution of grain sizes in the attenuation evaluation. Quantitative agreement between the experiment and the latter model was found in the Rayleigh and the Rayleigh-to-stochastic transition regions. A larger attenuation level was exhibited than the classical theoretical prediction considering a single mean grain size, and the frequency dependence of attenuation reduced from a classical fourth power to an approximately second power due to a greater probability of large grains than the assumed Poisson statistics. The provided results would help support the use of laser ultrasound technology for the non-destructive evaluation of grain size distribution in polycrystalline materials.
Study of Flexural Response in Strain Hardening Cementitious Composites Based on Proposed Parametric Model
Authors: Qi Zhanfeng , Huang Zhiyi , Li Hui , Chen Wenhua
Published: December 2018

Strain hardening cementitious composites (SHCCs) are widely used in projects due to their excellent deformation resistance and large energy absorption capacity. However, determining tensile strain capacity is still a challenge for engineers. The current popular approach is to use inverse methods to predict the tensile behavior of SHCCs, such as the UM method (Qian and Li) and the JCI (Japan Concrete Institute) method. The key to these two approaches is to acquire the exact relationship between the bending and the uniaxial response. In this paper, a reasonable linear constitutive model of the SHCCs is modified. Initially, the moment-curvature diagrams are discussed by material parameters. The results reveal that the moment-curvature response is quite sensitive to the variations in the parameter of transition strain α, post-cracking tensile stiffness η, and strain softening stiffness μ, however, for the compressive parameters, the moment-curvature responses influence on flexural behavior is insignificant. Moreover, the load-deflection curve in the mid-span of SHCC, based on the consideration of shear effect, is simulated under a four-point bending test (FPBT). The results show a remarkable consistency with the experimental data when compared to the previous simulations. It is expected that this modified method can enhance an accurate program in order to obtain the tensile capacity.
A Third Order Newton-Like Method and Its Applications
Authors: Sahu D. R. , Agarwal Ravi P. , Singh Vipin Kumar
Published: December 2018

In this paper, we design a new third order Newton-like method and establish its convergence theory for finding the approximate solutions of nonlinear operator equations in the setting of Banach spaces. First, we discuss the convergence analysis of our third order Newton-like method under the ω -continuity condition. Then we apply our approach to solve nonlinear fixed point problems and Fredholm integral equations, where the first derivative of an involved operator does not necessarily satisfy the Hölder and Lipschitz continuity conditions. Several numerical examples are given, which compare the applicability of our convergence theory with the ones in the literature.
Some Common Fixed Point Theorems for Generalized F-Contraction Involving w-Distance with Some Applications to Differential Equations
Authors: Mongkolkeha Chirasak , Gopal Dhananjay
Published: December 2018

In this paper, we introduce the Ćirić type generalized F-contraction and establish certain common fixed point results for such F-contraction in metric spaces with the w-distances. In addition, we give some examples to support our results. Finally, we apply our results to show the existence of solutions of the second order differential equation.
Alginate Materials and Dental Impression Technique: A Current State of the Art and Application to Dental Practice
Authors: Cervino Gabriele , Fiorillo Luca , Herford Alan Scott , Laino Luigi , Troiano Giuseppe , Amoroso Giulia , Crimi Salvatore , Matarese Marco , D’Amico Cesare , Nastro Siniscalchi Enrico , Cicciù Marco
Published: December 2018

Hydrocolloids were the first elastic materials to be used in the dental field. Elastic impression materials include reversible (agar-agar), irreversible (alginate) hydrocolloids and synthetic elastomers (polysulfides, polyethers, silicones). They reproduce an imprint faithfully, providing details of a high definition despite the presence of undercuts. With the removal of the impression, being particularly rich in water, the imprints can deform but later adapt to the original shape due to the elastic properties they possess. The advantages of using alginate include the low cost, a better tolerability on the part of the patient, the ease of manipulation, the short time needed for execution, the instrumentation and the very simple execution technique and possibility of detecting a detailed impression (even in the presence of undercuts) in a single step. A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed database. Authors conducted a search of articles in written in English published from 2008 to 2018. All the relevant studies were included in the search with respect to the characteristics and evolution of new marine derived materials. Much progress has been made in the search for new marine derived materials. Conventional impression materials are different, and especially with the advent of digital technology, they have been suffering from a decline in research attention over the last few years. However, this type of impression material, alginates (derived from marine algae), have the advantage of being among the most used in the dental medical field.
Natural Product Repertoire of the Genus Amphimedon
Authors: Shady Nourhan Hisham , Fouad Mostafa A. , Salah Kamel Mohamed , Schirmeister Tanja , Abdelmohsen Usama Ramadan
Published: December 2018

Marine sponges are a very attractive and rich source in the production of novel bioactive compounds. The sponges exhibit a wide range of pharmacological activities. The genus Amphimedon consists of various species, such as viridis, compressa, complanata, and terpenensis, along with a handful of undescribed species. The Amphimedon genus is a rich source of secondary metabolites containing diverse chemical classes, including alkaloids, ceramides, cerebrososides, and terpenes, with various valuable biological activities. This review covers the literature from January 1983 until January 2018 and provides a complete survey of all the compounds isolated from the genus Amphimedon and the associated microbiota, along with their corresponding biological activities, whenever applicable.
Effect of Vibration Stress Relief on the Shape Stability of Aluminum Alloy 7075 Thin-Walled Parts
Authors: Gong Hai , Sun Yanjie , Liu Yaoqiong , Wu Yunxin , He Yipeng , Sun Xiaoliang , Zhang Minghai
Published: December 2018

Aluminum alloy 7075 is one of the materials widely used in the manufacture of structural components used by aviation industries. High precision is required in producing the shapes of such components due to shape stability and dimensional accuracy being difficult to maintain throughout the different stages of manufacturing. In this work, an experimental study of the effect of VSR (Vibratory Stress Relief) on the deformation and residual stresses of aluminum alloy 7075 thin-walled components is presented. It was concluded that VSR improved the shape and size stability of the material to a significant level by relieving induced residual stresses in the thin-walled parts. Finally, more uniform residual stress distribution was obtained after the VSR treatment, compared to before the VSR treatment. This proved that VSR has a significant influence on improving the shape stability of the thin-walled aluminum alloy 7075 components.
Effect of the Tool Tilt Angle on the Heat Generation and the Material Flow in Friction Stir Welding
Authors: Dialami Narges , Cervera Miguel , Chiumenti Michele
Published: December 2018

This work studies the effect of the tool tilt angle on the generated heat and the material flow in the work pieces joint by Friction Stir Welding (FSW). An apropos kinematic framework together with a two-stage speed-up strategy is adopted to simulate the FSW problem. The effect of tilt angle on the FSWelds is modeled through the contact condition by modifying an enhanced friction model. A rotated friction shear stress is proposed, the angle of rotation depending on the process parameters and the tilt angle. The proposed rotation angle is calibrated by the experimental data provided for a tilt angle 2.5°. The differences of generated heat and material flow for the cases of tool with tilt angle of 0° and 2.5° are discussed. It is concluded that due to the higher temperature, softer material and greater frictional force in the trailing side of the tool, the material flow in the rear side of the FSW tool with the title angle is considerably enhanced, which assists to prevent the generation of defect.
PGE-Enrichment in Magnetite-Bearing Olivine Gabbro: New Observations from the Midcontinent Rift-Related Echo Lake Intrusion in Northern Michigan, USA
Authors: Koerber Alexander James , Thakurta Joyashish
Published: December 2018

The Echo Lake intrusion in the Upper Peninsula (UP) of Michigan, USA, was formed during the 1.1 Ga Midcontinent Rift event in North America. Troctolite is the predominant rock unit in the intrusion, with interlayered bands of peridotite, mafic pegmatitic rock, olivine gabbro, magnetite-bearing gabbro, and anorthosite. Exploratory drilling has revealed a platinum group element (PGE)-enriched zone within a 45 m thick magnetite-ilmenite-bearing olivine gabbro unit with grades up to 1.2 g/t Pt + Pd and 0.3 wt. % Cu. Fine, disseminated grains of sulfide minerals such as pyrrhotite and chalcopyrite occur in the mineralized interval. Formation of Cu-PGE-rich sulfide minerals might have been caused by sulfide melt saturation in a crystallizing magma, which was triggered by a sudden decrease in fO2 upon the crystallization and separation of titaniferous magnetite. This PGE-enriched zone is comparable to other well-known reef-like PGE deposits, such as the Sonju Lake deposit in northern Minnesota.
Application of Slag–Cement and Fly Ash for Strength Development in Cemented Paste Backfills
Authors: Zhao Yue , Soltani Amin , Taheri Abbas , Karakus Murat , Deng An
Published: December 2018

The present study investigates the combined capacity of a newly developed slag-blended cement (MC) and fly ash (FA) as a sustainable solution towards improving the mechanical performance of the cemented paste backfill (CPB) system of a copper-gold underground mine. A total of thirteen mix designs consisting of three MC-treated and ten MC + FA-treated blends were examined. Samples were prepared with a solids content of 77% (by total mass), and were allowed to cure for 7, 14, 28, 56 and 128 days prior unconfined compression testing. Scanning electron microscopy (SEM) studies were also carried out to observe the evolution of fabric in response to MC and MC + FA amendments. The greater the MC content and/or the longer the curing period, the higher the developed strength, toughness and stiffness. The exhibited improvements, however, were only notable up to 56 days of curing, beyond of which the effect of curing was marginal. The performance of 4% Portland cement or PC (by total dry mass) was found to be similar to that of 1.5% MC, while the higher MC inclusions of 2.5% and 3%, though lower in terms of binder content, unanimously outperformed 4% PC. The use of FA alongside MC improved the bonding/connection interface generated between the tailings aggregates, and thus led to improved mechanical performance compared with similar MC inclusions containing no FA. Common strength criteria for CPBs were considered to assess the applicability of the newly introduced MC and MC + FA mix designs. The mix designs “3% MC” and “2.5% MC + 2–2.5% FA” satisfied the 700 kPa strength threshold required for stope stability, and thus were deemed as optimum design choices.
Profile of Phosphatidylserine Modifications under Nitroxidative Stress Conditions Using a Liquid Chromatography-Mass Spectrometry Based Approach
Authors: Neves Bruna , Domingues Pedro , Oliveira Maria Manuel , Domingues Maria do Rosário , Melo Tânia
Published: December 2018

Nitrated lipids have been detected in vitro and in vivo, usually associated with a protective effect. While nitrated fatty acids have been widely studied, few studies reported the nitration and nitroxidation of the phospholipid classes phosphatidylcholine, and phosphatidylethanolamine. However, no information regarding nitrated and nitroxidized phosphatidylserine can be found in the literature. This work aims to identify and characterize the nitrated and nitroxidized derivatives of 1-palmitoyl-2-oleoyl-sn-3-glycero-phosphoserine (POPS), obtained after incubation with nitronium tetrafluoroborate, by liquid chromatography (LC) coupled to mass spectrometry (MS) and tandem MS (MS/MS). Several nitrated and nitroxidized products were identified, namely, nitro, nitroso, nitronitroso, and dinitro derivatives, as well as some nitroxidized species such as nitrosohydroxy, nitrohydroxy, and nitrohydroperoxy. The fragmentation pathways identified were structure-dependent and included the loss of HNO and HNO2 for nitroso and nitro derivatives, respectively. Combined losses of PS polar head group plus HNO or HNO2 and carboxylate anions of modified fatty acyl chain were also observed. The nitrated POPS also showed antiradical potential, demonstrated by the ability to scavenge the ABTS●+ and DPPH● radicals. Overall, this in vitro model of nitration based on LC-MS/MS provided additional insights into the nitrated and nitroxidized derivatives of PS and their fragmentation fingerprinting. This information is a valuable tool for targeted analysis of these modified PS in complex biological samples, to further explore the new clues on the antioxidant potential of nitrated POPS.
Shikonin Attenuates Acetaminophen-Induced Hepatotoxicity by Upregulation of Nrf2 through Akt/GSK3β Signaling
Authors: Li Huachao , Chen Yueming , Zhang Jiahao , Chen Xiangcui , Li Zheng , Liu Bing , Zhang Luyong
Published: December 2018

Acetaminophen (APAP) overdose-induced acute liver damage is mostly due to overwhelmingly increased oxidative stress. Nuclear factor-erythroid 2-related factor2 (Nrf2) plays an important role in alleviating APAP hepatic toxicity. Shikonin (SHK) enhances Nrf2 in multiple lines of normal cells. Nevertheless, whether SHK protects against APAP-induced liver toxicity remains undefined. This study found SHK defended APAP-induced liver toxicity, as well as reversed the levels of serum alanine/aspartate aminotransferases (ALT/AST), liver myeloperoxidase (MPO) activity, and reactive oxygen species (ROS), while it enhanced the liver glutathione (GSH) level in APAP-treated mice. SHK rescued the cell viability and GSH depletion, but neutralized oxidative stress in APAP-treated human normal liver L-02 cells. Mechanically, SHK increased Nrf2 expression in the exposure of APAP at the protein level but not at the mRNA level. Inhibition of Nrf2 blocked the SHK effect in APAP-treated hepatocytes. Furthermore, SHK improved Nrf2 stability through stimulating PI3K/Akt pathway, thus inhibiting GSK-3β. In vivo studies confirmed the close correlation of liver protection of SHK against APAP and Akt/GSK-3β/Nrf2 pathway. In conclusion, this study reveals that SHK prevents APAP hepatotoxicity by upregulation of Nrf2 via PI3K/Akt/GSK-3β pathway. Therefore, SHK may be a promising candidate against APAP-induced liver injury.
Basic Study of Drug-Drug Interaction between Memantine and the Traditional Japanese Kampo Medicine Yokukansan
Authors: Matsumoto Takashi , Sekiguchi Kyoji , Kawakami Zenji , Watanabe Junko , Mizoguchi Kazushige , Ikarashi Yasushi , Yamamoto Masahiro
Published: December 2018

Several basic pharmacokinetic and pharmacological studies were conducted as part of a group of studies to clarify the drug-drug interaction (DDI) between memantine (MEM), a drug used to treat Alzheimer’s disease, and yokukansan (YKS), a traditional Japanese Kampo medicine used to treat behavioral and psychological symptoms of dementia. The pharmacokinetic studies showed that there were no statistically significant differences in MEM concentrations in the plasma, brain, and urine between mice treated with MEM alone and with MEM plus YKS. Regarding candidate active ingredients of YKS, there were also no statistically significant differences in concentrations of geissoschizine methyl ether in the plasma and brain, urine, glycyrrhetinic acid in the plasma, and isoliquiritigenin in the urine, in mice treated with YKS alone or with MEM plus YKS. The pharmacological studies showed that isoliquiritigenin, which has an N-methyl-d-aspartic acid (NMDA) receptor antagonistic effect, did not affect the inhibitory effect of MEM on NMDA-induced intracellular Ca2+ influx in primary cultured rat cortical neurons. Moreover, YKS did not affect either the ameliorative effects of MEM on NMDA-induced learning and memory impairment, or the MEM-induced decrease in locomotor activities in mice. These results suggest that there is probably no pharmacokinetic or pharmacological interaction between MEM and YKS in mice, but more detailed studies are needed in the future. Our findings provide important information for future studies, to clarify the DDI more regarding the efficacy and safety of combined use of these drugs in a clinical situation.
Lignans in Spirits: Chemical Diversity, Quantification, and Sensory Impact of (±)-Lyoniresinol
Authors: Winstel Delphine , Marchal Axel
Published: December 2018

During barrel aging, spirits undergo organoleptic changes caused by the release of aroma and taste compounds. Recently, studies have revealed the bitter properties of oak wood lignans, such as (±)-lyoniresinol, and their contribution to wine taste. To evaluate the impact of lignans in spirits, a targeted screening of 11 compounds was set up and served to validate their presence in this matrix, implying their release by oak wood during aging. After development and validation of a quantification method, the most abundant and the bitterest lignan, (±)-lyoniresinol, was assayed by liquid chromatography–high resolution mass spectrometry (LC-HRMS) in spirits. Its gustatory detection threshold was established at 2.6 mg/L in spirits. A large number of samples quantified were above this detection threshold, which suggests its effect of increased bitterness in spirit taste. Significant variations were observed in commercial spirits, with concentrations ranging from 0.2 to 11.8 mg/L, which could be related to differences in barrel aging processes. In “eaux-de-vie” of cognac, concentrations of (±)-lyoniresinol were observed in the range from 1.6 mg/L to 12 mg/L. Lower concentrations were measured for older vintages.
Modulation of Skin Inflammatory Response by Active Components of Silymarin
Authors: Juráňová Jana , Aury-Landas Juliette , Boumediene Karim , Baugé Catherine , Biedermann David , Ulrichová Jitka , Franková Jana
Published: December 2018

In this study, we compared selected silymarin components, such as quercetin (QE), 2,3-dehydrosilybin (DHS) and silybin (SB), with the anti-inflammatory drug indomethacin (IND) in terms of their wound healing potential. In view of the fact that pathological cutaneous wound healing is associated with persistent inflammation, we studied their anti-inflammatory activity against inflammation induced by bacterial lipopolysaccharide (LPS). We investigated the regulation of crucial pro-inflammatory transcription factors—nuclear factor kappa-B (NF-κB) and activator protein 1 (AP-1)—as well as the expression of downstream inflammatory targets by Western blotting, real-time PCR (RT-PCR), electrophoretic mobility shift assay (EMSA), and/or enzyme-linked immunosorbent assay (ELISA) in vitro using primary normal human dermal fibroblasts (NHDF). We demonstrated the greater ability of DHS to modulate the pro-inflammatory cytokines production via the NF-κB and AP-1 signaling pathways when compared to other tested substances. The prolonged exposure of LPS-challenged human dermal fibroblasts to DHS had both beneficial and detrimental consequences. DHS diminished interleukin-6 (IL-6) and interleukin-8 (IL-8) secretion but induced the significant upregulation of IL-8 mRNA associated with NF-κB and AP-1 activation. The observed conflicting results may compromise the main expected benefit, which is the acceleration of the healing of the wound via a diminished inflammation.
Chemical Property Changes and Thermal Analysis during the Carbonizing Process of the Pollen Grains of Typha
Authors: Gao Mingliang , Bao Beihua , Cao Yudan , Shan Mingqiu , Cheng Fangfang , Jiang Miao , Chen Peidong , Zhang Li
Published: December 2018

Carbonized pollen grains of Typha (CPT) were widely used in clinical for antithrombosis, wound and bleeding in China. In order to ensure the role of drugs, it is very important to control the quality of drugs. However, there is a lack of monitoring methods in the process of charcoal preparation. To characterize the process of CPT, we used thermal analysis, scanning electron microscope (SEM), color measurement, Fourier transform infrared spectrometry (FTIR) and HPLC. In this study, 7 min was the optimal processing time and the heating process condition should be controlled under 272.35 ± 7.23 °C. This comprehensive strategy to depict the whole carbonizing process would provide new ideas for researches on quality control of Traditional Chinese Medicine (TCM) and processing theory of charcoal medicine.
Anxiolytic Effects of Acanthopanax senticosus HARMS Occur via Regulation of Autonomic Function and Activate Hippocampal BDNF–TrkB Signaling
Authors: Miyazaki Shouhei , Oikawa Hirotaka , Takekoshi Hideo , Hoshizaki Masako , Ogata Masato , Fujikawa Takahiko
Published: December 2018

Mental stress, such as anxiety and conflict, causes physiological changes, such as changes in autonomic nervous activity and gastric ulcers. In addition, stress induces glucocorticoids and changes the hippocampal brain-derived neurotrophic factor (BDNF) expression levels. We previously reported that Acanthopanax senticosus HARM (ASH) prevents stress-induced gastric ulcers. Thus, we investigated the potential anxiolytic effect and influence of ASH on the hippocampus BDNF-related protein in male Sprague-Dawley rats fed 1% and 5% ASH extract-containing food for one week using novelty suppressed feeding (NSF) and improved elevated beam walking (IEBW) tests. ASH treatment significantly decreased latency to eat in the NSF test and increased the time spent on the open arm in the IEBW test. ASH5% treatment showed a significant decrease in LFnu, indicative of sympathetic nervous activity, and a significant increase in HFnu, indicative of parasympathetic nervous activity, in the NSF test. In addition, ASH1% and ASH5% treatments significantly decreased LFnu and significantly increased HFnu in the IEBW test. ASH5% treatment significantly increased hippocampal BDNF protein expression in both Western blotting and immunohistochemistry experiments. Our findings suggest that anxiolytic effects of ASH occur via the regulation of autonomic function and increased hippocampal BDNF signaling.
Effective Tetradentate Compound Complexes against Leishmania spp. that Act on Critical Enzymatic Pathways of These Parasites
Authors: Urbanová Kristína , Ramírez-Macías Inmaculada , Martín-Escolano Rubén , Rosales María José , Cussó Olaf , Serrano Joan , Company Anna , Sánchez-Moreno Manuel , Costas Miquel , Ribas Xavi , Marín Clotilde
Published: December 2018

The spectrum and efficacy of available antileishmanial drugs is limited. In the present work we evaluated in vitro the antiproliferative activity of 11 compounds based on tetradentate polyamines compounds against three Leishmania species (L. braziliensis, L. donovani and L. infantum) and the possible mechanism of action. We identified six compounds (3, 5, 6, 7, 8 and 10) effective against all three Leishmania spp both on extracellular and intracellular forms. These six most active leishmanicidal compounds also prevent the infection of host cells. Nevertheless, only compound 7 is targeted against the Leishmania SOD. Meanwhile, on the glucose metabolism the tested compounds have a species-specific effect on Leishmania spp.: L. braziliensis was affected mainly by 10 and 8, L. donovani by 7, and L. infantum by 5 and 3. Finally, the cellular ultrastructure was mainly damaged by 11 in the three Leishmania spp. studied. These identified antileishmania candidates constitute a good alternative treatment and will be further studied.
Small Polar Molecules: A Challenge in Marine Chemical Ecology
Authors: Ternon Eva , Wang Yanfei , Coyne Kathryn J.
Published: December 2018

Due to increasing evidence of key chemically mediated interactions in marine ecosystems, a real interest in the characterization of the metabolites involved in such intra and interspecific interactions has emerged over the past decade. Nevertheless, only a small number of studies have succeeded in identifying the chemical structure of compounds of interest. One reason for this low success rate is the small size and extremely polar features of many of these chemical compounds. Indeed, a major challenge in the search for active metabolites is the extraction of small polar compounds from seawater. Yet, a full characterization of those metabolites is necessary to understand the interactions they mediate. In this context, the study presented here aims to provide a methodology for the characterization of highly polar, low molecular weight compounds in a seawater matrix that could provide guidance for marine ecologists in their efforts to identify active metabolites. This methodology was applied to the investigation of the chemical structure of an algicidal compound secreted by the bacteria Shewanella sp. IRI-160 that was previously shown to induce programmed cell death in dinoflagellates. The results suggest that the algicidal effects may be attributed to synergistic effects of small amines (ammonium, 4-aminobutanal) derived from the catabolization of putrescine produced in large quantities (0.05–6.5 fmol/cell) by Shewanella sp. IRI-160.
Selection of Reference Genes for qRT-PCR Analysis in Lentinula edodes after Hot-Air Drying
Authors: Gao Shuangshuang , Wang Gangzheng , Huang Zhicheng , Lei Xiaoyu , Bian Yinbing , Liu Ying , Huang Wen
Published: December 2018

Volatile sulfur compounds gradually develop in Lentinula edodes after hot-air drying, and many genes are involved in the generation of these sulfur compounds. The expression stability of reference genes may vary in a particular experimental treatment when analyzing their expressions by quantitative real-time polymerase chain reaction (qRT-PCR). In this study, the expression profile of 17 candidate genes was assessed in L. edodes under treatment at 50 °C for 0, 1, 2, and 3 h, and the expression stability of each reference gene was analyzed by three statistical algorithms, including geNorm, NormFinder, and BestKeeper. Results indicated that the two optimal reference genes for mycelium and fruiting body were CAC and DAHP as well as CAC and NUP, respectively. Additionally, CAC and DAHP were found to be the two most stable reference genes across the mycelium and fruiting body set. Our results will provide a genetic foundation for further research on the metabolism genes of sulfur compounds in L. edodes.
Herb–Drug Interaction Potential of Anti-Borreliae Effective Extracts from Uncaria tomentosa (Samento) and Otoba parvifolia (Banderol) Assessed In Vitro
Authors: Weiss Johanna
Published: December 2018

Samento (extract from Uncaria tomentosa) and Banderol (extract from Otoba parvifolia) have been demonstrated to have anti-inflammatory and antimicrobial properties, e.g., against different morphological forms of Borrelia burgdorferi. However, there is hardly any data on the pharmacological safety of these two herbal medicines. This in vitro study aimed at scrutinizing their possible characteristics as perpetrators in pharmacokinetic herbal–drug interactions. Inhibition of cytochrome P450 enzymes (CYPs) was quantified by commercial kits and inhibition of drug transporters by use of fluorescent probe substrates. Induction was quantified by real-time RT-PCR and activation of pregnane x receptor (PXR) and aryl hydrocarbon receptor (AhR) by reporter gene assays. Organic anion transporting polypeptide 1B1 (OATP1B1) (IC50 = 0.49 ± 0.28%) and OATP1B3 (IC50 = 0.65 ± 0.29%) were potently inhibited by Banderol, but only weakly by Samento. CYP3A4 was inhibited about 40% at a Samento concentration of 1%. Samento significantly induced mRNA expression of CYP2J2, UGT1A3, UGT1A9, ABCB1, and SLCO1B1 and strongly activated PXR, but hardly AhR. In conclusion, the perpetrator profiles of Samento and Banderol for herb–drug interactions completely differ. Clinical studies are strongly recommended to clarify whether the effects observed in vitro are of clinical relevance.
Linear Birefringent Films of Cellulose Nanocrystals Produced by Dip-Coating
Authors: Mendoza-Galván Arturo , Tejeda-Galán Tania , Domínguez-Gómez Amos B. , Mauricio-Sánchez Reina Araceli , Järrendahl Kenneth , Arwin Hans
Published: December 2018

Transparent films of cellulose nanocrystals (CNC) are prepared by dip-coating on glass substrates from aqueous suspensions of hydrolyzed filter paper. Dragging forces acting during films’ deposition promote a preferential alignment of the rod-shaped CNC. Films that are 2.8 and 6.0 µm in thickness show retardance effects, as evidenced by placing them between a linearly polarized light source and a linear polarizer sheet in the extinction configuration. Transmission Mueller matrix spectroscopic ellipsometry measurements at normal incidence as a function of sample rotation were used to characterize polarization properties. A differential decomposition of the Mueller matrix reveals linear birefringence as the unique polarization parameter. These results show a promising way for obtaining CNC birefringent films by a simple and controllable method.
Androgen and Oestrogen Affect the Expression of Long Non-Coding RNAs During Phallus Development in a Marsupial
Authors: Chen Yu , Kuroki Yoko , Shaw Geoff , Pask Andrew J. , Yu Hongshi , Toyoda Atsushi , Fujiyama Asao , Renfree Marilyn B.
Published: December 2018

There is increasing evidence that long non-coding RNAs (lncRNAs) are important for normal reproductive development, yet very few lncRNAs have been identified in phalluses so far. Unlike eutherians, phallus development in the marsupial tammar wallaby occurs post-natally, enabling manipulation not possible in eutherians in which differentiation occurs in utero. We treated with sex steroids to determine the effects of androgen and oestrogen on lncRNA expression during phallus development. Hormonal manipulations altered the coding and non-coding gene expression profile of phalluses. We identified several predicted co-regulatory lncRNAs that appear to be co-expressed with the hormone-responsive candidate genes regulating urethral closure and phallus growth, namely IGF1, AR and ESR1. Interestingly, more than 50% of AR-associated coding genes and lncRNAs were also associated with ESR1. In addition, we identified and validated three novel co-regulatory and hormone-responsive lncRNAs: lnc-BMP5, lnc-ZBTB16 and lncRSPO4. Lnc-BMP5 was detected in the urethral epithelium of male phalluses and was downregulated by oestrogen in males. Lnc-ZBTB16 was downregulated by oestrogen treatment in male phalluses at day 50 post-partum (pp). LncRSPO4 was downregulated by adiol treatment in female phalluses but increased in male phalluses after castration. Thus, the expression pattern and hormone responsiveness of these lncRNAs suggests a physiological role in the development of the phallus.
Improved Preventive Effects of Combined Bioactive Compounds Present in Different Blueberry Varieties as Compared to Single Phytochemicals
Authors: Van Breda Simone G. J. , Briedé Jacob J. , De Kok Theo M. C. M.
Published: December 2018

Blueberries contain many different phytochemicals which might be responsible for their disease preventive properties. In a previously conducted human dietary intervention study, we showed that a 4-week intervention with blueberry–apple juice protected the participants against oxidative stress and modulated expression of genes involved in different genetic pathways contributing to the antioxidant response. The present study investigates the effect of different blueberry varieties (Elliot, Draper, Bluecrop, and Aurora, and the blueberry–apple juice from our previous human dietary intervention study), and four different single compounds (vitamin C, peonidin, cyanidin, and quercetin) on antioxidant capacity and gene expression changes in colonic cells in vitro, and compares the outcome with the earlier in vivo findings. The results demonstrate that all blueberry varieties as well as the blueberry–apple juice were more effective in reducing oxidative stress as compared to the single compounds (e.g., DNA strand break reduction: EC50: Elliot 8.3 mg/mL, Aurora and Draper 11.9 mg/mL, blueberry–apple juice 12.3 mg/mL, and Bluecrop 12.7 mg/mL; single compounds). In addition, the gene expression profiles (consisting of 18 selected genes from the in vivo study) induced by the blueberry varieties were more similar to the profile of the human intervention study (range 44–78%). The blueberry variety Elliot showed the strongest and most similar effects, almost 80% of gene expression modulations were similar compared to the in vivo results. From the single compounds (range 17–44%), quercetin induced the most comparable gene expression changes, i.e., 44%. This approach could be useful in agriculture for identifying crop varieties containing combinations of phytochemicals which show optimal preventive capacities.
Tart Cherry Prevents Bone Loss through Inhibition of RANKL in TNF-Overexpressing Mice
Authors: Moon Nicholas , Effiong Linda , Song Lee , Gardner Thomas R. , Soung Do Y.
Published: December 2018

Current drugs for the treatment of rheumatoid arthritis-associated bone loss come with concerns about their continued use. Thus, it is necessary to identify natural products with similar effects, but with fewer or no side effects. We determined whether tart cherry (TC) could be used as a supplement to prevent inflammation-mediated bone loss in tumor necrosis factor (TNF)-overexpressing transgenic (TG) mice. TG mice were assigned to a 0%, 5%, or 10% TC diet, with a group receiving infliximab as a positive control. Age-matched wild-type (WT) littermates fed a 0% TC diet were used as a normal control. Mice were monitored by measurement of body weight. Bone health was evaluated via serum biomarkers, microcomputed tomography (µCT), molecular assessments, and mechanical testing. TC prevented TNF-mediated weight loss, while it did not suppress elevated levels of interleukin (IL)-1β and IL-6. TC also protected bone structure from inflammation-induced bone loss with a reduced ratio of receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) to a degree comparable to infliximab. Furthermore, unlike with infliximab, TC exhibited a moderate improvement in TNF-mediated decline in bone stiffness. Thus, TC could be used as a prophylactic regimen against future fragility fractures in the context of highly chronic inflammation.
Pharmacokinetic Simulations of Intravitreal Biologicals: Aspects of Drug Delivery to the Posterior and Anterior Segments
Authors: Rimpelä Anna-Kaisa , Kiiski Iiro , Deng Feng , Kidron Heidi , Urtti Arto
Published: December 2018

Biologicals are important ocular drugs that are be delivered using monthly and bimonthly intravitreal injections to treat retinal diseases, such as age-related macular degeneration. Long acting delivery systems are needed for prolongation of their dosing interval. Intravitreal biologicals are eliminated from the eye via the aqueous humor outflow. Thus, the anterior and posterior segments are exposed to the drug. We utilized a kinetic simulation model to estimate protein drug concentrations in the vitreous and aqueous humor after bolus injection and controlled release administration to the vitreous. The simulations predicted accurately the experimental levels of 5 biologicals in the vitreous and aqueous humor. The good match between the simulations and experimental data demonstrated almost complete anterior segment bioavailability, and major dose sparing with ocular controlled release systems. Overall, the model is a useful tool in the design of intraocular delivery of biologicals.
Development of Multifunctional Liposomes Containing Magnetic/Plasmonic MnFe2O4/Au Core/Shell Nanoparticles
Authors: Rodrigues Ana Rita O. , Matos Joana O. G. , Nova Dias Armando M. , Almeida Bernardo G. , Pires Ana , Pereira André M. , Araújo João P. , Queiroz Maria-João R. P. , Castanheira Elisabete M. S. , Coutinho Paulo J. G.
Published: December 2018

Multifunctional liposomes containing manganese ferrite/gold core/shell nanoparticles were developed. These magnetic/plasmonic nanoparticles were covered by a lipid bilayer or entrapped in liposomes, which form solid or aqueous magnetoliposomes as nanocarriers for simultaneous chemotherapy and phototherapy. The core/shell nanoparticles were characterized by UV/Visible absorption, X-Ray Diffraction (XRD), Transmission Electron Microscopy (TEM), and Superconducting Quantum Interference Device (SQUID). The magnetoliposomes were characterized by Dynamic Light Scattering (DLS) and TEM. Fluorescence-based techniques (FRET, steady-state emission, and anisotropy) investigated the incorporation of a potential anti-tumor drug (a thienopyridine derivative) in these nanosystems. The core/shell nanoparticles exhibit sizes of 25 ± 2 nm (from TEM), a plasmonic absorption band (λmax = 550 nm), and keep magnetic character. XRD measurements allowed for the estimation of 13.3 nm diameter for manganese ferrite core and 11.7 nm due to the gold shell. Aqueous magnetoliposomes, with hydrodynamic diameters of 152 ± 18 nm, interact with model membranes by fusion and are able to transport the anti-tumor compound in the lipid membrane, with a high encapsulation efficiency (EE (%) = 98.4 ± 0.8). Solid magnetoliposomes exhibit hydrodynamic diameters around 140 nm and also carry successfully the anticancer drug (with EE (%) = 91.2 ± 5.2), while also being promising as agents for phototherapy. The developed multifunctional liposomes can be promising as therapeutic agents for combined chemo/phototherapy.
Optical, Electrical and Thermal Properties of Organic–Inorganic Hybrids with Conjugated Polymers Based on POSS Having Heterogeneous Substituents
Authors: Ueda Kazunari , Tanaka Kazuo , Chujo Yoshiki
Published: December 2018

Preparation of organic–inorganic hybrids with conventional conjugated polymers such as polyfluorene (PF) and poly(3-hexylthiophene) (P3HT) were demonstrated via the facile blending in solution by employing polyhedral oligomeric silsesquioxane (POSS) having heterogeneous alkyl substituents. From the optical measurements, it was shown that the modified POSS derivatives played a critical role in facilitating amorphous state of polymer matrices. Interestingly, although inter-strand interaction decreased after POSS addition in the hybrid films, thermal stability can be enhanced in the presence of the modified POSS with long alkyl chains. Furthermore, it was demonstrated that carrier mobilities through the hybrid film was minimally reduced by POSS. These results suggest that POSS should be a versatile building block to form hybrid with various types of polymers for enhancing durability without loss of electronic properties of organic components.