bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjustment of Dysregulated Ceramide Metabolism in a Murine Model of Sepsis-Induced Cardiac Dysfunction
Authors: Chung Ha-Yeun , Kollmey Anna , Schrepper Andrea , Kohl Matthias , Bläss Markus , Stehr Sebastian , Lupp Amelie , Gräler Markus , Claus Ralf
Published: April 2017

Cardiac dysfunction, in particular of the left ventricle, is a common and early event in sepsis, and is strongly associated with an increase in patients’ mortality. Acid sphingomyelinase (SMPD1)—the principal regulator for rapid and transient generation of the lipid mediator ceramide—is involved in both the regulation of host response in sepsis as well as in the pathogenesis of chronic heart failure. This study determined the degree and the potential role to which SMPD1 and its modulation affect sepsis-induced cardiomyopathy using both genetically deficient and pharmacologically-treated animals in a polymicrobial sepsis model. As surrogate parameters of sepsis-induced cardiomyopathy, cardiac function, markers of oxidative stress as well as troponin I levels were found to be improved in desipramine-treated animals, desipramine being an inhibitor of ceramide formation. Additionally, ceramide formation in cardiac tissue was dysregulated in SMPD1+/+ as well as SMPD1−/− animals, whereas desipramine pretreatment resulted in stable, but increased ceramide content during host response. This was a result of elevated de novo synthesis. Strikingly, desipramine treatment led to significantly improved levels of surrogate markers. Furthermore, similar results in desipramine-pretreated SMPD1−/− littermates suggest an SMPD1-independent pathway. Finally, a pattern of differentially expressed transcripts important for regulation of apoptosis as well as antioxidative and cytokine response supports the concept that desipramine modulates ceramide formation, resulting in beneficial myocardial effects. We describe a novel, protective role of desipramine during sepsis-induced cardiac dysfunction that controls ceramide content. In addition, it may be possible to modulate cardiac function during host response by pre-conditioning with the Food and Drug Administration (FDA)-approved drug desipramine.
Interplay between Oxidative Stress and Nutrient Sensing Signaling in the Developmental Origins of Cardiovascular Disease
Authors: Tain You-Lin , Hsu Chien-Ning
Published: April 2017

Cardiovascular disease (CVD) presents a global health burden, despite recent advances in management. CVD can originate from early life by so-called “developmental origins of health and disease” (DOHaD). Epidemiological and experimental evidence supports that early-life insults can induce programming of later CVD. Underlying the DOHaD concept, early intervention may offset programming process to prevent the development of CVD, namely reprogramming. Oxidative stress and nutrient sensing signals have been considered to be major mechanisms of cardiovascular programming, while the interplay between these two mechanisms have not been examined in detail. This review summarizes current evidence that supports the link between oxidative stress and nutrient sensing signaling to cardiovascular programming, with an emphasis on the l-arginine–asymmetric dimethylarginine (ADMA)–nitric oxide (NO) pathway. This review provides an overview of evidence from human studies supporting fetal programming of CVD, insight from animal models of cardiovascular programming and oxidative stress, impact of the l-arginine–ADMA–NO pathway in cardiovascular programming, the crosstalk between l-arginine metabolism and nutrient sensing signals, and application of reprogramming interventions to prevent the programming of CVD. A greater understanding of the mechanisms underlying cardiovascular programming is essential to developing early reprogramming interventions to combat the globally growing epidemic of CVD.
Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via Regulation of TLR4 and PPAR-γ Dependent on PI3K/Akt/mTOR Signal Pathway
Authors: Sun Haijian , Zhu Xuexue , Cai Weiwei , Qiu Liying
Published: April 2017

Endothelial lesion response to injurious stimuli is a necessary step for initiating inflammatory cascades in blood vessels. Hypaphorine (Hy) from different marine sources is shown to exhibit anti-inflammatory properties. However, the potential roles and possible molecular mechanisms of Hy in endothelial inflammation have yet to be fully clarified. We showed that Hy significantly inhibited the positive effects of lipopolysaccharide (LPS) on pro-inflammatory cytokines expressions, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemoattractant protein 1 (MCP-1) and vascular cellular adhesion molecule-1 (VCAM-1), as well as induction of the phosphorylation of Akt and mTOR in HMEC-1 cells. The downregulated peroxisome proliferator-activated receptor γ (PPAR-γ) and upregulated toll-like receptor 4 (TLR4) expressions in LPS-challenged endothelial cells were prevented by Hy. Inhibition of both PI3K and mTOR reversed LPS-stimulated increases in TLR4 expressions and decreases in PPAR-γ levels. Genetic silencing of TLR4 or PPAR-γ agonist pioglitazone obviously abrogated the levels of pro-inflammatory cytokines in LPS-treated HMEC-1 cells. These results suggest that Hy may exert anti-inflammatory actions through the regulation of TLR4 and PPAR-γ dependent on PI3K/Akt/mTOR signal pathways. Hy may be considered as a therapeutic agent that can potentially relieve or ameliorate endothelial inflammation-associated diseases.
Comparative Study of Blood-Based Biomarkers, α2,3-Sialic Acid PSA and PHI, for High-Risk Prostate Cancer Detection
Authors: Ferrer-Batallé Montserrat , Llop Esther , Ramírez Manel , Aleixandre Rosa , Saez Marc , Comet Josep , De Llorens Rafael , Peracaula Rosa
Published: April 2017

Prostate Specific Antigen (PSA) is the most commonly used serum marker for prostate cancer (PCa), although it is not specific and sensitive enough to allow the differential diagnosis of the more aggressive tumors. For that, new diagnostic methods are being developed, such as PCA-3, PSA isoforms that have resulted in the 4K score or the Prostate Health Index (PHI), and PSA glycoforms. In the present study, we have compared the PHI with our recently developed PSA glycoform assay, based on the determination of the α2,3-sialic acid percentage of serum PSA (% α2,3-SA), in a cohort of 79 patients, which include 50 PCa of different grades and 29 benign prostate hyperplasia (BPH) patients. The % α2,3-SA could distinguish high-risk PCa patients from the rest of patients better than the PHI (area under the curve (AUC) of 0.971 vs. 0.840), although the PHI correlated better with the Gleason score than the % α2,3-SA. The combination of both markers increased the AUC up to 0.985 resulting in 100% sensitivity and 94.7% specificity to differentiate high-risk PCa from the other low and intermediate-risk PCa and BPH patients. These results suggest that both serum markers complement each other and offer an improved diagnostic tool to identify high-risk PCa, which is an important requirement for guiding treatment decisions.
Transcriptome Sequencing of Dianthus spiculifolius and Analysis of the Genes Involved in Responses to Combined Cold and Drought Stress
Authors: Zhou Aimin , Ma Hongping , Liu Enhui , Jiang Tongtong , Feng Shuang , Gong Shufang , Wang Jingang
Published: April 2017

Dianthus spiculifolius, a perennial herbaceous flower and a member of the Caryophyllaceae family, has strong resistance to cold and drought stresses. To explore the transcriptional responses of D. spiculifolius to individual and combined stresses, we performed transcriptome sequencing of seedlings under normal conditions or subjected to cold treatment (CT), simulated drought treatment (DT), or their combination (CTDT). After de novo assembly of the obtained reads, 112,015 unigenes were generated. Analysis of differentially expressed genes (DEGs) showed that 2026, 940, and 2346 genes were up-regulated and 1468, 707, and 1759 were down-regulated in CT, DT, and CTDT samples, respectively. Among all the DEGs, 182 up-regulated and 116 down-regulated genes were identified in all the treatment groups. Analysis of metabolic pathways and regulatory networks associated with the DEGs revealed overlaps and cross-talk between cold and drought stress response pathways. The expression profiles of the selected DEGs in CT, DT, and CTDT samples were characterized and confirmed by quantitative RT-PCR. These DEGs and metabolic pathways may play important roles in the response of D. spiculifolius to the combined stress. Functional characterization of these genes and pathways will provide new targets for enhancement of plant stress tolerance through genetic manipulation.
Pannexin- and Connexin-Mediated Intercellular Communication in Platelet Function
Authors: Molica Filippo , Stierlin Florian , Fontana Pierre , Kwak Brenda
Published: April 2017

The three major blood cell types, i.e., platelets, erythrocytes and leukocytes, are all produced in the bone marrow. While red blood cells are the most numerous and white cells are the largest, platelets are small fragments and account for a minor part of blood volume. However, platelets display a crucial function by preventing bleeding. Upon vessel wall injury, platelets adhere to exposed extracellular matrix, become activated, and form a platelet plug preventing hemorrhagic events. However, when platelet activation is exacerbated, as in rupture of an atherosclerotic plaque, the same mechanism may lead to acute thrombosis causing major ischemic events such as myocardial infarction or stroke. In the past few years, major progress has been made in understanding of platelet function modulation. In this respect, membrane channels formed by connexins and/or pannexins are of particular interest. While it is still not completely understood whether connexins function as hemichannels or gap junction channels to inhibit platelet aggregation, there is clear-cut evidence for a specific implication of pannexin1 channels in collagen-induced aggregation. The focus of this review is to summarize current knowledge of the role of connexins and pannexins in platelet aggregation and to discuss possible pharmacological approaches along with their limitations and future perspectives for new potential therapies.
Fisetin Protects PC12 Cells from Tunicamycin-Mediated Cell Death via Reactive Oxygen Species Scavenging and Modulation of Nrf2-Driven Gene Expression, SIRT1 and MAPK Signaling in PC12 Cells
Authors: Yen Jui-Hung , Wu Pei-Shan , Chen Shu-Fen , Wu Ming-Jiuan
Published: April 2017

Background: Fisetin (3,7,3′,4′-tetrahydroxyflavone) is a dietary flavonol and exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However, high concentration of fisetin is reported to produce reactive oxygen species (ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer cells. The aim of this study is to investigate the cytoprotective effects of low concentration of fisetin against tunicamycin (Tm)-mediated cytotoxicity in neuronal-like catecholaminergic PC12 cells. Methods: Cell viability was assayed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and apoptotic and autophagic markers were analyzed by Western blot. Gene expression of unfolded protein response (UPR) and Phase II enzymes was further investigated using RT-Q-PCR or Western blotting. Intracellular ROS level was measured using 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) by a fluorometer. The effects of fisetin on mitogen activated protein kinases (MAPKs) and SIRT1 (Sirtuin 1) signaling pathways were examined using Western blotting and specific inhibitors. Results: Fisetin (<20 µM) restored cell viability and repressed apoptosis, autophagy and ROS production in Tm-treated cells. Fisetin attenuated Tm-mediated expression of ER stress genes, such as glucose-regulated proteins 78 (GRP78), C/EBP homologous protein (CHOP also known as GADD153) and Tribbles homolog 3 (TRB3), but induced the expression of nuclear E2 related factor (Nrf)2-targeted heme oxygenase (HO)-1, glutamate cysteine ligase (GCL) and cystine/glutamate transporter (xCT/SLC7A11), in both the presence and absence of Tm. Moreover, fisetin enhanced phosphorylation of ERK (extracellular signal-regulated kinase), JNK (c-JUN NH2-terminal protein kinase), and p38 MAPK. Addition of JNK and p38 MAPK inhibitor significantly antagonized its cytoprotective activity and modulatory effects on UPR. Fisetin also restored Tm-inhibited SIRT1 expression and addition of sirtinol (SIRT1 activation inhibitor) significantly blocked fisetin-mediated cytoprotection. In conclusion, this result shows that fisetin activates Nrf2, MAPK and SIRT1, which may elicit adaptive cellular stress response pathways so as to protect cells from Tm-induced cytotoxicity.
Silk Fibroin-Alginate-Hydroxyapatite Composite Particles in Bone Tissue Engineering Applications In Vivo
Authors: Jo You-Young , Kim Seong-Gon , Kwon Kwang-Jun , Kweon HaeYong , Chae Weon-Sik , Yang Won-Geun , Lee Eun-Young , Seok Hyun
Published: April 2017

The aim of this study was to evaluate the in vivo bone regeneration capability of alginate (AL), AL/hydroxyapatite (HA), and AL/HA/silk fibroin (SF) composites. Forty Sprague Dawley rats were used for the animal experiments. Central calvarial bone (diameter: 8.0 mm) defects were grafted with AL, AL/HA, or AL/HA/SF. New bone formation was evaluated by histomorphometric analysis. To demonstrate the immunocompatibility of each group, the level of tumor necrosis factor (TNF)-α expression was studied by immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) at eight weeks post implantation. Additionally, osteogenic markers, such as fibroblast growth factor (FGF)-23, osteoprotegerin (OPG), and Runt-related transcription factor (Runx2) were evaluated by qPCR or IHC at eight weeks post implantation. The AL/HA/SF group showed significantly higher new bone formation than did the control group (p = 0.044) and the AL group (p = 0.035) at four weeks post implantation. Additionally, the AL/HA/SF group showed lower relative TNF-α mRNA levels and higher FGF-23 mRNA levels than the other groups did at eight weeks post implantation. IHC results demonstrated that the AL/HA/SF group had lower TNF-α expression and higher OPG and Runx2 expression at eight weeks post implantation. Additionally, no evidence of the inflammatory reaction or giant cell formation was observed around the residual graft material. We concluded that the AL/HA/SF composite could be effective as a scaffold for bone tissue engineering.
BBDS: Blockchain-Based Data Sharing for Electronic Medical Records in Cloud Environments
Authors: Xia Qi , Sifah Emmanuel , Smahi Abla , Amofa Sandro , Zhang Xiaosong
Published: April 2017

Disseminating medical data beyond the protected cloud of institutions poses severe risks to patients’ privacy, as breaches push them to the point where they abstain from full disclosure of their condition. This situation negatively impacts the patient, scientific research, and all stakeholders. To address this challenge, we propose a blockchain-based data sharing framework that sufficiently addresses the access control challenges associated with sensitive data stored in the cloud using immutability and built-in autonomy properties of the blockchain. Our system is based on a permissioned blockchain which allows access to only invited, and hence verified users. As a result of this design, further accountability is guaranteed as all users are already known and a log of their actions is kept by the blockchain. The system permits users to request data from the shared pool after their identities and cryptographic keys are verified. The evidence from the system evaluation shows that our scheme is lightweight, scalable, and efficient.
Modeling Future Urban Sprawl and Landscape Change in the Laguna de Bay Area, Philippines
Authors: Iizuka Kotaro , Johnson Brian A. , Onishi Akio , Magcale-Macandog Damasa B. , Endo Isao , Bragais Milben
Published: April 2017

This study uses a spatially-explicit land-use/land-cover (LULC) modeling approach to model and map the future (2016–2030) LULC of the area surrounding the Laguna de Bay of Philippines under three different scenarios: ‘business-as-usual’, ‘compact development’, and ‘high sprawl’ scenarios. The Laguna de Bay is the largest lake in the Philippines and an important natural resource for the population in/around Metro Manila. The LULC around the lake is rapidly changing due to urban sprawl, so local and national government agencies situated in the area need an understanding of the future (likely) LULC changes and their associated hydrological impacts. The spatial modeling approach involved three main steps: (1) mapping the locations of past LULC changes; (2) identifying the drivers of these past changes; and (3) identifying where and when future LULC changes are likely to occur. Utilizing various publically-available spatial datasets representing potential drivers of LULC changes, a LULC change model was calibrated using the Multilayer Perceptron (MLP) neural network algorithm. After calibrating the model, future LULC changes were modeled and mapped up to the year 2030. Our modeling results showed that the ‘built-up’ LULC class is likely to experience the greatest increase in land area due to losses in ‘crop/grass’ (and to a lesser degree ‘tree’) LULC, and this is attributed to continued urban sprawl.
Comparative Efficacies of Collagen-Based 3D Printed PCL/PLGA/β-TCP Composite Block Bone Grafts and Biphasic Calcium Phosphate Bone Substitute for Bone Regeneration
Authors: Hwang Kyoung-Sub , Choi Jae-Won , Kim Jae-Hun , Chung Ho , Jin Songwan , Shim Jin-Hyung , Yun Won-Soo , Jeong Chang-Mo , Huh Jung-Bo
Published: April 2017

The purpose of this study was to compare bone regeneration and space maintaining ability of three-dimensional (3D) printed bone grafts with conventional biphasic calcium phosphate (BCP). After mixing polycaprolactone (PCL), poly (lactic-co-glycolic acid) (PLGA), and β-tricalcium phosphate (β-TCP) in a 4:4:2 ratio, PCL/PLGA/β-TCP particulate bone grafts were fabricated using 3D printing technology. Fabricated particulate bone grafts were mixed with atelocollagen to produce collagen-based PCL/PLGA/β-TCP composite block bone grafts. After formation of calvarial defects 8 mm in diameter, PCL/PLGA/β-TCP composite block bone grafts and BCP were implanted into bone defects of 32 rats. Although PCL/PLGA/β-TCP composite block bone grafts were not superior in bone regeneration ability compared to BCP, the results showed relatively similar performance. Furthermore, PCL/PLGA/β-TCP composite block bone grafts showed better ability to maintain bone defects and to support barrier membranes than BCP. Therefore, within the limitations of this study, PCL/PLGA/β-TCP composite block bone grafts could be considered as an alternative to synthetic bone grafts available for clinical use.
Prediction of First-Year Corrosion Losses of Carbon Steel and Zinc in Continental Regions
Authors: Panchenko Yulia , Marshakov Andrey
Published: April 2017

Dose-response functions (DRFs) developed for the prediction of first-year corrosion losses of carbon steel and zinc (K1) in continental regions are presented. The dependences of mass losses on SO2 concentration, K = f([SO2]), obtained from experimental data, as well as nonlinear dependences of mass losses on meteorological parameters, were taken into account in the development of the DRFs. The development of the DRFs was based on the experimental data from one year of testing under a number of international programs: ISO CORRAG, MICAT, two UN/ECE programs, the Russian program in the Far-Eastern region, and data published in papers. The paper describes predictions of K1 values of these metals using four different models for continental test sites under UN/ECE, RF programs and within the MICAT project. The predictions of K1 are compared with experimental K1 values, and the models presented here are analyzed in terms of the coefficients used in the models.
Room-Temperature and High-Temperature Tensile Mechanical Properties of TA15 Titanium Alloy and TiB Whisker-Reinforced TA15 Matrix Composites Fabricated by Vacuum Hot-Pressing Sintering
Authors: Feng Yangju , Zhang Wencong , Zeng Li , Cui Guorong , Chen Wenzhen
Published: April 2017

In this paper, the microstructure, the room-temperature and high-temperature tensile mechanical properties of monolithic TA15 alloy and TiB whisker-reinforced TA15 titanium matrix composites (TiBw/TA15) fabricated by vacuum hot-pressing sintering were investigated. The microstructure results showed that there were no obvious differences in the microstructure between monolithic TA15 alloy and TiBw/TA15 composites, except whether or not the grain boundaries contained TiBw. After sintering, the matrix microstructure presented a typical Widmanstätten structure and the size of primary β grain was consistent with the size of spherical TA15 titanium metallic powders. This result demonstrated that TiBw was not the only factor limiting grain coarsening of the primary β grain. Moreover, the grain coarsening of α colonies was obvious, and high-angle grain boundaries (HAGBs) were distributed within the primary β grain. In addition, TiBw played an important role in the microstructure evolution. In the composites, TiBw were randomly distributed in the matrix and surrounded by a large number of low-angle grain boundaries (LAGBs). Globularization of α phase occurred prior, near the TiBw region, because TiBw provided the nucleation site for the equiaxed α phase. The room-temperature and high-temperature tensile results showed that TiBw distributed at the primary β grain boundaries can strengthen the grain boundary, but reduce the connectivity of the matrix. Therefore, compared to the monolithic TA15 alloy fabricated by the same process, the tensile strength of the composites increased, and the tensile elongation decreased. Moreover, with the addition of TiBw, the fracture mechanism was changed to a mixture of brittle fracture and ductile failure (composites) from ductile failure (monolithic TA15 alloy). The fracture surfaces of TiBw/TA15 composites were the grain boundaries of the primary β grain where the majority of TiB whiskers distributed, i.e., the surfaces of the spherical TA15 titanium metallic powders.
Automated Cable Preparation for Robotized Stator Cable Winding
Authors: Hultman Erik , Leijon Mats
Published: April 2017

A method for robotized cable winding of the Uppsala University Wave Energy Converter generator stator has previously been presented and validated. The purpose of this study is to present and validate further developments to the method: automated stand-alone equipment for the preparation of the winding cables. The cable preparation consists of three parts: feeding the cable from a drum, forming the cable end and cutting the cable. Forming and cutting the cable was previously done manually and only small cable drums could be handled. Therefore the robot cell needed to be stopped frequently. The new equipment was tested in an experimental robot stator cable winding setup. Through the experiments, the equipment was validated to be able to perform fully automated and robust cable preparation. Suggestions are also given on how to further develop the equipment with regards to performance, robustness and quality. Hence, this work represents another important step towards demonstrating completely automated robotized stator cable winding.
Advanced Plasticity Modeling for Ultra-Low-Cycle-Fatigue Simulation of Steel Pipe
Authors: Li Rongting , Eyckens Philip , E Daxin , Gawad Jerzy , Poucke Maarten , Cooreman Steven , Bael Albert
Published: April 2017

Pipelines and piping components may be exposed to extreme loading conditions, for instance earthquakes and hurricanes. In such conditions, they undergo severe plastic strains, which may locally reach the fracture limits due to either monotonic loading or ultra-low cycle fatigue (ULCF). Aiming to investigate the failure process and strain evolution of pipes enduring ULCF, a lab-scale ULCF test on an X65 steel pipeline component is simulated with finite element models, and experimental data are used to validate various material modeling assumptions. The paper focuses on plastic material modeling and compares different models for plastic anisotropy in combination with various hardening models, including isotropic, linear kinematic and combined hardening models. Both isotropic and anisotropic assumptions for plastic yielding are considered. As pipes pose difficulty for the measurement of plastic properties in mechanical testing, we calibrate an anisotropic yield locus using advanced multi-scale simulation based on texture measurements. Moreover, the importance of the anisotropy gradient across thickness is studied in detail for this thick-walled pipeline steel. It is found that the usage of a combined hardening model is essential to accurately predict the number of the cycles until failure, as well as the strain evolution during the fatigue test. The advanced hardening modeling featuring kinematic hardening has a substantially higher impact on result accuracy compared to the yield locus assumption for the studied ULCF test. Cyclic tension-compression testing is conducted to calibrate the kinematic hardening models. Additionally, plastic anisotropy and its gradient across the thickness play a notable, yet secondary role. Based on this research, it is advised to focus on improvements in strain hardening characteristics in future developments of pipeline steel with enhanced earthquake resistance.
Paper-Based Analytical Device for Zinc Ion Quantification in Water Samples with Power-Free Analyte Concentration
Authors: Kudo Hiroko , Yamada Kentaro , Watanabe Daiki , Suzuki Koji , Citterio Daniel
Published: April 2017

Insufficient sensitivity is a general issue of colorimetric paper-based analytical devices (PADs) for trace analyte detection, such as metal ions, in environmental water. This paper demonstrates the colorimetric detection of zinc ions (Zn2+) on a paper-based analytical device with an integrated analyte concentration system. Concentration of Zn2+ ions from an enlarged sample volume (1 mL) has been achieved with the aid of a colorimetric Zn2+ indicator (Zincon) electrostatically immobilized onto a filter paper substrate in combination with highly water-absorbent materials. Analyte concentration as well as sample pretreatment, including pH adjustment and interferent masking, has been elaborated. The resulting device enables colorimetric quantification of Zn2+ in environmental water samples (tap water, river water) from a single sample application. The achieved detection limit of 0.53 μM is a significant improvement over that of a commercial colorimetric Zn2+ test paper (9.7 μM), demonstrating the efficiency of the developed analyte concentration system not requiring any equipment.
Ultrahigh-Throughput Improvement and Discovery of Enzymes Using Droplet-Based Microfluidic Screening
Authors: Autour Alexis , Ryckelynck Michael
Published: April 2017

Enzymes are extremely valuable tools for industrial, environmental, and biotechnological applications and there is a constant need for improving existing biological catalysts and for discovering new ones. Screening microbe or gene libraries is an efficient way of identifying new enzymes. In this view, droplet-based microfluidics appears to be one of the most powerful approaches as it allows inexpensive screenings in well-controlled conditions and an ultrahigh-throughput regime. This review aims to introduce the main microfluidic devices and concepts to be considered for such screening before presenting and discussing the latest successful applications of the technology for enzyme discovery.
A Micromanipulator and Transporter Based on Vibrating Bubbles in an Open Chip Environment
Authors: Dai Liguo , Jiao Niandong , Wang Xiaodong , Liu Lianqing
Published: April 2017

A novel micromanipulation technique of multi-objectives based on vibrating bubbles in an open chip environment is described in this paper. Bubbles were created in an aqueous medium by the thermal energy converted from a laser. When the piezoelectric stack fixed under the chip vibrated the bubbles, micro-objects (microparticles, cells, etc.) rapidly moved towards the bubbles. Results from numerical simulation demonstrate that convective flow around the bubbles can provide forces to capture objects. Since bubbles can be generated at arbitrary destinations in the open chip environment, they can act as both micromanipulators and transporters. As a result, micro- and bio-objects could be collected and transported effectively as masses in the open chip environment. This makes it possible for scientific instruments, such as atomic force microscopy (AFM) and scanning ion conductive microscopy (SICM), to operate the micro-objects directly in an open chip environment.
The Effect of Citrus Essential Oils and Their Constituents on Growth of Xanthomonas citri subsp. citri
Authors: Mirzaei-Najafgholi Hossein , Tarighi Saeed , Golmohammadi Morteza , Taheri Parissa
Published: April 2017

Citrus bacterial canker (CBC) caused by Xanthomonas citri subsp. citri (Xcc), is the most devastating of the citrus diseases worldwide. During our study, we found that Essential oils (EOs) of some citrus cultivars are effective on Xcc. Therefore, it prompted us to determine the plant metabolites responsible for the antibacterial properties. We obtained EOs from some locally cultivated citrus by using a Clevenger apparatus and their major constituents were identified by gas chromatography/mass spectrometry (GC-MS). The effect of Citrus aurantium, C. aurantifolia, Fortunella sp. EOs and their major constituents were evaluated against Xcc-KVXCC1 using a disk diffusion assay. Minimal inhibitory and bactericidal concentration of the EOs and their constituents were determined using the broth microdilution method. C. aurantium, C. aurantifolia Eos, and their major constituents including citral, linalool, citronellal, geraniol, α-terpineol, and linalyl acetate indicated antibacterial effects against Xcc. The C. aurantifolia EO and citral showed the highest antibacterial activity among the tested EOs and constituents with inhibition zones of 15 ± 0.33 mm and 16.67 ± 0.88 mm, respectively. Synergistic effects of the constituents were observed between α-terpineol-citral, citral-citronellal, citral-geraniol, and citronellal-geraniol by using a microdilution checkerboard assay. Transmission electron microscopy revealed that exposure of Xcc cells to citral caused cell wall damage and altered cytoplasmic density. We introduced C. aurantifolia and C. aurantium EOs, and their constituents citral, α-terpineol, citronellal, geraniol, and linalool as possible control agents for CBC.
Bioavailable Citrus sinensis Extract: Polyphenolic Composition and Biological Activity
Authors: Pepe Giacomo , Pagano Francesco , Adesso Simona , Sommella Eduardo , Ostacolo Carmine , Manfra Michele , Chieppa Marcello , Sala Marina , Russo Mariateresa , Marzocco Stefania , Campiglia Pietro
Published: April 2017

Citrus plants contain large amounts of flavonoids with beneficial effects on human health. In the present study, the antioxidant and anti-inflammatory potential of bioavailable polyphenols from Citrus sinensis was evaluated in vitro and ex vivo, using the murine macrophages cell line J774A.1 and primary peritoneal macrophages. Following simulated gastro-intestinal digestion, the in vitro bioavailability of Citrus sinensis polyphenolic extract was assessed using the human cell line Caco-2 grown as monolayers on a transwell membrane. Data demonstrated a relative permeation of its compounds (8.3%). Thus, the antioxidant and anti-inflammatory effect of polyphenolic Citrus sinensis fraction (Cs) was compared to the bioavailable one (CsB). Results revealed that Citrus extract were able to reduce macrophages pro-inflammatory mediators, including nitric oxide, iNOS, COX-2 and different cytokines. Moreover, the effect of Citrus sinensis polyphenols was associated with antioxidant effects, such as a reduction of reactive oxygen species (ROS) and heme-oxygenase-1 (HO-1) increased expression. Our results provide evidence that the bioavailable polyphenolic constituents of the Citrus sinensis extract accumulate prevalently at intestinal level and could reach systemic circulation exerting their effect. The bioavailable fraction showed a higher anti-inflammatory and antioxidant potential compared to the initial extract, thus highlighting its potential nutraceutical value.
Synthesis of Curcuminoids and Evaluation of Their Cytotoxic and Antioxidant Properties
Authors: Lozada-García María , Enríquez Raúl , Ramírez-Apán Teresa , Nieto-Camacho Antonio , Palacios-Espinosa Juan , Custodio-Galván Zeltzin , Soria-Arteche Olivia , Pérez-Villanueva Jaime
Published: April 2017

Curcumin (1) and ten derivatives (2–11) were synthesized and evaluated as cytotoxic and antioxidant agents. The results of primary screening by Sulforhodamine B assay against five human cancer cell lines (U-251 MG, glioblastoma; PC-3, human prostatic; HCT-15, human colorectal; K562, human chronic myelogenous leukemia; and SKLU-1, non-small cell lung cancer) allowed us to calculate the half maximal inhibitory concentration (IC50) values for the more active compounds against HCT-15 and K562 cell lines. Compounds 2 and 10 were the most active against both cell lines and were more active than curcumin itself. Thiobarbituric acid reactive substances (TBARS) assay showed that 7 has potent activity; even stronger than curcumin, α-tocopherol, and quercetin.
Synthesis and Spectral Properties of meso-Arylbacteriochlorins, Including Insights into Essential Motifs of their Hydrodipyrrin Precursors
Authors: Reddy Muthyala , Zhang Shaofei , Kim Han-Je , Mass Olga , Taniguchi Masahiko , Lindsey Jonathan
Published: April 2017

Synthetic bacteriochlorins—analogues of bacteriochlorophylls, Nature’s near-infrared absorbers—are attractive for diverse photochemical studies. meso-Arylbacteriochlorins have been prepared by the self-condensation of a dihydrodipyrrin–carbinol or dihydrodipyrrin–acetal following an Eastern-Western (E-W) or Northern-Southern (N-S) joining process. The bacteriochlorins bear a gem-dimethyl group in each pyrroline ring to ensure stability toward oxidation. The two routes differ in the location of the gem-dimethyl group at the respective 3- or 2-position in the dihydrodipyrrin, and the method of synthesis of the dihydrodipyrrin. Treatment of a known 3,3-dimethyldihydrodipyrrin-1-carboxaldehyde with an aryl Grignard reagent afforded the dihydrodipyrrin-1-(aryl)carbinol, and upon subsequent acetylation, the corresponding dihydrodipyrrin-1-methyl acetate (dihydrodipyrrin–acetate). Self-condensation of the dihydrodipyrrin–acetate gave a meso-diarylbacteriochlorin (E-W route). A 2,2-dimethyl-5-aryldihydrodipyrrin-1-(aryl)carbinol underwent self-condensation to give a trans-A2B2-type meso-tetraarylbacteriochlorin (N-S route). In each case, the aromatization process entails a 2e−/2H+ (aerobic) dehydrogenative oxidation following the dihydrodipyrrin self-condensation. Comparison of a tetrahydrodipyrrin–acetal (0%) versus a dihydrodipyrrin–acetal (41%) in bacteriochlorin formation and results with various 1-substituted dihydrodipyrrins revealed the importance of resonance stabilization of the reactive hydrodipyrrin intermediate. Altogether 10 new dihydrodipyrrins and five new bacteriochlorins have been prepared. The bacteriochlorins exhibit characteristic bacteriochlorophyll-like absorption spectra, including a Qy band in the region 726–743 nm.
Na+i,K+i-Dependent and -Independent Signaling Triggered by Cardiotonic Steroids: Facts and Artifacts
Authors: Orlov Sergei , Klimanova Elizaveta , Tverskoi Artem , Vladychenskaya Elizaveta , Smolyaninova Larisa , Lopina Olga
Published: April 2017

Na+,K+-ATPase is the only known receptor of cardiotonic steroids (CTS) whose interaction with catalytic α-subunits leads to inhibition of this enzyme. As predicted, CTS affect numerous cellular functions related to the maintenance of the transmembrane gradient of monovalent cations, such as electrical membrane potential, cell volume, transepithelial movement of salt and osmotically-obliged water, symport of Na+ with inorganic phosphate, glucose, amino acids, nucleotides, etc. During the last two decades, it was shown that side-by-side with these canonical Na+i/K+i-dependent cellular responses, long-term exposure to CTS affects transcription, translation, tight junction, cell adhesion and exhibits tissue-specific impact on cell survival and death. It was also shown that CTS trigger diverse signaling cascades via conformational transitions of the Na+,K+-ATPase α-subunit that, in turn, results in the activation of membrane-associated non-receptor tyrosine kinase Src, phosphatidylinositol 3-kinase and the inositol 1,4,5-triphosphate receptor. These findings allowed researchers to propose that endogenous CTS might be considered as a novel class of steroid hormones. We focus our review on the analysis of the relative impact Na+i,K+i-mediated and -independent pathways in cellular responses evoked by CTS.
Stability of Bioactive Compounds in Broccoli as Affected by Cutting Styles and Storage Time
Authors: Torres-Contreras Ana Mariel , Nair Vimal , Cisneros-Zevallos Luis , Jacobo-Velázquez Daniel A.
Published: April 2017

Broccoli contains bioactive molecules and thus its consumption is related with the prevention of chronic and degenerative diseases. The application of wounding stress to horticultural crops is a common practice, since it is the basis for the fresh-cut produce industry. In this study, the effect of four different cutting styles (CSs) (florets (CS1), florets cut into two even pieces (CS2), florets cut into four even pieces (CS3), and florets processed into chops (CS4)) and storage time (0 and 24 h at 20 °C) on the content of bioactive compounds in broccoli was evaluated. Immediately after cutting, 5-O-caffeoylquinic acid and caffeic acid content increased by 122.4% and 41.6% in CS4 and CS2, respectively. Likewise, after storage, 3-O-caffeoylquinic acid and 5-O-caffeoylquinic acid increased by 46.7% and 98.2%, respectively in CS1. Glucoerucin and gluconasturtiin content decreased by 62% and 50%, respectively in CS3; whereas after storage most glucosinolates increased in CS1. Total isothiocyanates, increased by 133% immediately in CS4, and after storage CS1 showed 65% higher levels of sulforaphane. Total ascorbic acid increased 35% after cutting in CS2, and remained stable after storage. Results presented herein would allow broccoli producers to select proper cutting styles that preserve or increase the content of bioactive molecules.
Optimization of Ultrasound-Assisted Extraction of Antioxidants from the Mung Bean Coat
Authors: Zhou Yue , Zheng Jie , Gan Ren-You , Zhou Tong , Xu Dong-Ping , Li Hua-Bin
Published: April 2017

Mung bean (Vigna radiata) sprout is commonly consumed as a vegetable, while the coat of the germinated mung bean is a waste. In this paper, an ultrasound-assisted extraction method has been developed to extract natural antioxidants from the seed coat of mung bean. Several experimental parameters—which included ethanol concentration, solvent/material ratio, ultrasound extraction time, temperature, and power—were studied in single-factor experiments. The interaction of three key experimental parameters (ethanol concentration, solvent/material ratio, and ultrasonic extraction time) was further investigated by response surface method. Besides, traditional extracting methods, including maceration and Soxhlet extraction methods, were also carried out for comparison. The results suggested that the best extracting condition was 37.6% (v/v) of ethanol concentration, 35.1:1 mL/g of solvent/material ratio and ultrasonic extraction of 46.1 min at 70 °C under 500 W ultrasonic irradiation. The antioxidant capacity (178.28 ± 7.39 µmol Trolox/g DW) was much stronger than those obtained by the maceration extraction process (158.66 ± 4.73 µmol Trolox/g DW) and the Soxhlet extraction process (138.42 ± 3.63 µmol Trolox/g DW). In addition, several antioxidant components in the extract were identified and quantified. This study is helpful for value-added utilization of the waste from germinated mung bean.
Systematic Understanding of the Mechanism of Salvianolic Acid A via Computational Target Fishing
Authors: Chen Shao-Jun , Cui Ming-Chao
Published: April 2017

Salvianolic acid A (SAA) is one of the most abundant water-soluble and potent anti-oxidative compounds isolated from Danshen, a traditional Chinese medicine. A systematic overview of its mechanism of action is yet to be performed. In the present study, the druggability of SAA was measured using the TCMSP server, and potential targets of SAA were identified by PharmMapper and DRAR-CPI. Intersecting targets were then assessed by GeneMANIA and GO pathway analysis, and drug-target-pathway networks were constructed to give a visual view. The results showed that SAA has good druggability, and 13 putative protein targets were identified. Network analysis showed that these targets were associated with cancer, metabolism and other physiological processes. In summary, SAA is predicted to target multiple proteins and pathways to form a network that exerts systematic pharmacological effects.
Molecular Hybridization-Guided One-Pot Multicomponent Synthesis of Turmerone Motif-Fused 3,3′-Pyrrolidinyl-dispirooxindoles via a 1,3-Dipolar Cycloaddition Reaction
Authors: Lin Bing , Zhou Gen , Gong Yi , Wei Qi-Di , Tian Min-Yi , Liu Xiong-Li , Feng Ting-Ting , Zhou Ying , Yuan Wei-Cheng
Published: April 2017

Described herein is the development of a facile and efficient methodology for the synthesis of novel turmerone motif-fused 3,3′-pyrrolidinyl-dispirooxindoles 3–5 via a multicomponent 1,3-dipolar cycloaddition of dienones 2 with azomethine ylides (thermally generated in situfrom isatins and proline or thioproline or sarcosine). Products bearing four or three consecutive stereocenters consist of two oxindole moieties and a pyrrolidinyl core, including vicinal spiroquaternary stereocenters fused in one ring structure were smoothly obtained in high yields (up to 93% yield) with good diastereoselectivity (up to >20:1). Another valuable application of this method was for the design of new hybrid architectures for biological screening through the adequate fusion of these sub-units of turmerone and 3,3′-pyrrolidinyl-dispirooxindole, generating drug-like molecules.
Chemical Constituents of Supercritical Extracts from Alpinia officinarum and the Feeding Deterrent Activity against Tribolium castaneum
Authors: Xin Mintong , Guo Shanshan , Zhang Wenjuan , Geng Zhufeng , Liang Junyu , Du Shushan , Deng Zhiwei , Wang Yongyan
Published: April 2017

Alpinia officinarum has been confirmed to possess bioactivities against some pests. In this work, a sample was obtained from A. officinarum rhizomes by supercritical fluid CO2 extraction (SFE). According to GC-MS analysis, the main chemical components for SFE-sample included benzylacetone (26.77%), 1,7-diphenyl-5-hydroxy-3-heptanone (17.78%), guaiacylacetone (10.03%) and benzenepropanal (7.42%). The essential oil of A. officinarum rhizomes (LD50 = 20.71 μg/adult) exhibited more contact toxicity than SFE extract (LD50 = 82.72 μg/adult) against Tribolium castaneum. From SFE extracts, one new compound, 1-phenyl-4-(16,17-dimethyl-9,13-octadiene)-5-isopentenyl-7-(4”-methoxyl-3”-hydroxyl-phenyl)-3-heptanone (3), together with five known compounds identified as 5-hydroxy-1,7-diphenyl-3-heptanone (1), 1,7-diphenyl-4-hepten-3-one (2), galangin (4), galangin-3-methyl ether (5) and pinocembrin (6), were isolated and their feeding deterrent activities against T. castaneum adults were assessed. It was found that compounds 1–6 had feeding deterrent activities against T. castaneum with feeding deterrent indices of 18.21%, 18.94%, 19.79%, 26.99%, 20.34%, and 35.81%, respectively, at the concentration of 1500 ppm. Hence, the essential oil and SFE extracts/compounds of A. officinarum rhizomes represent promising alternatives in the control of T. castaneum adults.
Parenteral Nutrition and Lipids
Authors: Raman Maitreyi , Almutairdi Abdulelah , Mulesa Leanne , Alberda Cathy , Beattie Colleen , Gramlich Leah
Published: April 2017

Lipids have multiple physiological roles that are biologically vital. Soybean oil lipid emulsions have been the mainstay of parenteral nutrition lipid formulations for decades in North America. Utilizing intravenous lipid emulsions in parenteral nutrition has minimized the dependence on dextrose as a major source of nonprotein calories and prevents the clinical consequences of essential fatty acid deficiency. Emerging literature has indicated that there are benefits to utilizing alternative lipids such as olive/soy-based formulations, and combination lipids such as soy/MCT/olive/fish oil, compared with soybean based lipids, as they have less inflammatory properties, are immune modulating, have higher antioxidant content, decrease risk of cholestasis, and improve clinical outcomes in certain subgroups of patients. The objective of this article is to review the history of IVLE, their composition, the different generations of widely available IVLE, the variables to consider when selecting lipids, and the complications of IVLE and how to minimize them.
Oleuropein Decreases Cyclooxygenase-2 and Interleukin-17 Expression and Attenuates Inflammatory Damage in Colonic Samples from Ulcerative Colitis Patients
Authors: Larussa Tiziana , Oliverio Manuela , Suraci Evelina , Greco Marta , Placida Roberta , Gervasi Serena , Marasco Raffaella , Imeneo Maria , Paolino Donatella , Tucci Luigi , Gulletta Elio , Fresta Massimo , Procopio Antonio , Luzza Francesco
Published: April 2017

Oleuropein (OLE) is the major phenolic secoiridoid of olive tree leaves, and its antioxidant and anti-inflammatory activities have been demonstrated in in vitro and in vivo animal models. The aim of this study was to investigate the activity of OLE in the colonic mucosa from patients with ulcerative colitis (UC). Biopsies obtained during colonoscopy from 14 patients with active UC were immediately placed in an organ culture chamber and challenged with lipopolysaccharide from Escherichia coli (EC-LPS) at 1 μg/mL in the presence or absence of 3 mM OLE. The expression of cyclooxygenase (COX)-2 and interleukin (IL)-17 was assessed in total protein extracts from treated colonic biopsies by Western blotting. Levels of IL-17 were also measured in culture supernatant by ELISA. A microscopic evaluation of the cultured biopsies was performed by conventional histology and immunohistochemistry. The expression of COX-2 and IL-17 were significantly lower in samples treated with OLE + EC-LPS compared with those treated with EC-LPS alone (0.80 ± 0.15 arbitrary units (a.u.) vs. 1.06 ± 0.19 a.u., p = 0.003, and 0.71 ± 0.08 a.u. vs. 1.26 ± 0.42 a.u., p = 0.03, respectively) as were the levels of IL-17 in culture supernatants of OLE + EC-LPS treated colonic samples (21.16 ± 8.64 pg/mL vs. 40.67 ± 9.24 pg/mL, p = 0.01). Histologically, OLE-treated colonic samples showed an amelioration of inflammatory damage with reduced infiltration of CD3, CD4, and CD20 cells, while CD68 numbers increased. The anti-inflammatory activity of OLE was demonstrated in colonic biopsies from UC patients. These new data support a potential role of OLE in the treatment of UC.