bluuebunny/crossref_metadata_2025 huggingface dataset:
CMV-Specific Immune Response—New Patients, New Insight: Central Role of Specific IgG during Infancy and Long-Lasting Immune Deficiency after Allogenic Stem Cell Transplantation
Authors: Zdziarski Przemyslaw
Published: January 2019

Although the existing paradigm states that cytomegalovirus (CMV) reactivation is under the control of the cellular immune response, the role of humoral and innate counterparts are underestimated. The study analyzed the host–virus interaction i.e., CMV-immune response evolution during infection in three different clinical situations: (1) immunodeficient CMV-positive human leukocyte antigen (HLA)-matched bone marrow recipients after immunoablative conditioning as well as immunocompetent, (2) adult, and (3) infant with primary immune response. In the first situation, a fast and significant decrease of specific immunity was observed but reconstitution of marrow-derived B and natural killer (NK) cells was observed prior to thymic origin of T cells. The lowest CMV-IgG (93.2 RU/mL) was found just before CMV viremia. It is noteworthy that the sole and exclusive factor of CMV-specific immune response is a residual recipient antibody class IgG. The CMV-quantiferon increase was detected later, but in the first phase, phytohemagglutinin (PHA)-induced IFN-γ release was significantly lower than that of CMV-induced (“indeterminate” results). It corresponds with the increase of NK cells at the top of lymphocyte reconstitution and undetected CMV-specific CD8 cells using a pentamer technique. In immunocompetent adult (CMV-negative donor), the cellular and humoral immune response increased in a parallel manner, but symptoms of CMV mononucleosis persisted until the increase of specific IgG. During infancy, the decrease of the maternal CMV-IgG level to 89.08 RU/mL followed by clinical sequel, i.e., CMV replication, were described. My observations shed light on a unique host-CMV interaction and CMV-IgG role: they indicate that its significant decrease predicts CMV replication. Before primary cellular immune response development, the high level of residual CMV-IgG (about >100 R/mL) from mother or recipient prevents virus reactivation. The innate immune response and NK-dependent IFN-secretion should be further investigated.
Infection of Embryonic Callus with Agrobacterium Enables High-Speed Transformation of Maize
Authors: Du Dengxiang , Jin Ruchang , Guo Jinjie , Zhang Fangdong
Published: January 2019

Several approaches have recently been adopted to improve Agrobacterium-mediated transformation of maize; however, about eight months of in vitro culture are still required to isolate transgenic plants. Furthermore, genetic transformation of maize depends on immature embryos, which greatly increases costs. Here, we report a method that ensures the competency of an embryogenic callus secondary culture under laboratory conditions for Agrobacterium-mediated transformation. Moreover, pretreatment of the cell wall with a mixed lytic enzyme solution prior to Agrobacterium infection, significantly improved transformation efficiency and stability. Average stable transformation efficiency was approximately 30.39%, with peaks of 94.46%. Expression and phenotypic analysis of the Rsc reporter gene were tested in the T0 generation of transgenic plants. Using this system, we successfully regenerated transgenic maize plantlets within three months of the emergence of the embryogenic callus. Additionally, we reduced somaclonal variation accompanying prolonged culture of maize cells in the dedifferentiated state, thus facilitating the molecular breeding of maize.
Fluorescence Quenching-Based Mechanism for Determination of Hypochlorite by Coumarin-Derived Sensors
Authors: Starzak Karolina , Matwijczuk Arkadiusz , Creaven Bernadette , Matwijczuk Alicja , Wybraniec Sławomir , Karcz Dariusz
Published: January 2019

A fluorescence quenching-based mechanism for the determination of hypochlorite was proposed based on spectroscopic and chromatographic studies on the hypochlorite-sensing potency of three structurally similar and highly fluorescent coumarins. The mode of action was found to rely upon a chlorination of the coumarin-based probes resulting from their reaction with sodium hypochlorite. Importantly, the formation of chlorinated derivatives was accompanied by a linear decrease in the fluorescence intensities of the probes tested. The results obtained suggest the applicability of a coumarin-dependent hypochlorite recognition mechanism for the detection of, as well as for quantitative determination of, hypochlorite species in vitro.
Molecular Mechanisms of Leucine Zipper EF-Hand Containing Transmembrane Protein-1 Function in Health and Disease
Authors: Lin Qi-Tong , Stathopulos Peter B.
Published: January 2019

Mitochondrial calcium (Ca2+) uptake shapes cytosolic Ca2+ signals involved in countless cellular processes and more directly regulates numerous mitochondrial functions including ATP production, autophagy and apoptosis. Given the intimate link to both life and death processes, it is imperative that mitochondria tightly regulate intramitochondrial Ca2+ levels with a high degree of precision. Among the Ca2+ handling tools of mitochondria, the leucine zipper EF-hand containing transmembrane protein-1 (LETM1) is a transporter protein localized to the inner mitochondrial membrane shown to constitute a Ca2+/H+ exchanger activity. The significance of LETM1 to mitochondrial Ca2+ regulation is evident from Wolf-Hirschhorn syndrome patients that harbor a haplodeficiency in LETM1 expression, leading to dysfunctional mitochondrial Ca2+ handling and from numerous types of cancer cells that show an upregulation of LETM1 expression. Despite the significance of LETM1 to cell physiology and pathophysiology, the molecular mechanisms of LETM1 function remain poorly defined. In this review, we aim to provide an overview of the current understanding of LETM1 structure and function and pinpoint the knowledge gaps that need to be filled in order to unravel the underlying mechanistic basis for LETM1 function.
Growth Factor Quantification of Platelet-Rich Plasma in Burn Patients Compared to Matched Healthy Volunteers
Authors: Marck Roos E. , Gardien Kim L. M. , Vlig Marcel , Breederveld Roelf S. , Middelkoop Esther
Published: January 2019

Platelet rich plasma (PRP) is blood plasma with a platelet concentration above baseline. When activated, PRP releases growth factors involved in all stages of wound healing, potentially boosting the healing process. To expand our knowledge of the effectiveness of PRP, it is crucial to know the content and composition of PRP products. In this study, growth factor quantification measurements of PRP from burn patients and gender- and age-matched controls were performed. The PRP of burn patients showed levels of growth factors comparable to those of the PRP of healthy volunteers. Considerable intra-individual variation in growth factor content was found. However, a correlation was found between the platelet count of the PRP and most of the growth factors measured.
Nutraceutical and Medicinal Potential of the Morus Species in Metabolic Dysfunctions
Authors: Rodrigues Elisana Lima , Marcelino Gabriela , Silva Gabriela Torres , Figueiredo Priscila Silva , Garcez Walmir Silva , Corsino Joaquim , Guimarães Rita de Cássia Avellaneda , Freitas Karine de Cássia
Published: January 2019

Many populations use medicinal plants as a therapeutic treatment, due to their lower cost and greater access. Among the plant species used for medicinal purposes are those of the genus Morus. The most known species are Morus alba, rubra, and nigra. This review aims to collect data from the literature, predominantly from cell and animal studies, which presents a possible nutraceutical and medicinal potential of the species Morus for use in metabolic dysfunctions. The fruits and leaves of mulberry are used for therapeutic purposes. For scientific confirmation of these effects, they were studied for laxative properties, antibacterial activity, anti-atherogenic activity, and hepatoprotective function. Furthermore, the genus Morus is recognized for the treatment and prevention of diabetes mellitus, through its hypoglycemic action. It may also provide health benefits through immunomodulatory, anti-inflammatory, and anti-nociceptive effects. It has been found that the Morus species have phenolic compounds, flavonoids, and anthocyanins that act as important antioxidants and promote beneficial effects on human health. These phytochemical compounds differ among species. Blackberry (Morus nigra) are rich in flavonoids, while the white mulberry (Morus alba) has low concentrations of flavonoids and anthocyanins. In addition, another important factor is to ensure a complete exemption of toxic risks in the use of medicinal plants for the treatment of diseases. Studies have shown no toxic effects by the administration of extracts of Morus species. Thus, the mulberry tree presents nutraceutical potential. It is therefore a promising alternative for medicinal products based on medicinal plants.
KSIMC: Predicting Kinase–Substrate Interactions Based on Matrix Completion
Authors: Gan Jingzhong , Qiu Jie , Deng Canshang , Lan Wei , Chen Qingfeng , Hu Yanling
Published: January 2019

Protein phosphorylation is an important chemical modification catalyzed by kinases. It plays important roles in many cellular processes. Predicting kinase–substrate interactions is vital to understanding the mechanism of many diseases. Many computational methods have been proposed to identify kinase–substrate interactions. However, the prediction accuracy still needs to be improved. Therefore, it is necessary to develop an efficient computational method to predict kinase–substrate interactions. In this paper, we propose a novel computational approach, KSIMC, to identify kinase–substrate interactions based on matrix completion. Firstly, the kinase similarity and substrate similarity are calculated by aligning sequence of kinase–kinase and substrate–substrate, respectively. Then, the original association network is adjusted based on the similarities. Finally, the matrix completion is used to predict potential kinase–substrate interactions. The experiment results show that our method outperforms other state-of-the-art algorithms in performance. Furthermore, the relevant databases and scientific literature verify the effectiveness of our algorithm for new kinase–substrate interaction identification.
NMDA Receptors in Astrocytes: In Search for Roles in Neurotransmission and Astrocytic Homeostasis
Authors: Skowrońska Katarzyna , Obara-Michlewska Marta , Zielińska Magdalena , Albrecht Jan
Published: January 2019

Studies of the last two decades have demonstrated the presence in astrocytic cell membranes of N-methyl-d-aspartate (NMDA) receptors (NMDARs), albeit their apparently low abundance makes demonstration of their presence and function more difficult than of other glutamate (Glu) receptor classes residing in astrocytes. Activation of astrocytic NMDARs directly in brain slices and in acutely isolated or cultured astrocytes evokes intracellular calcium increase, by mutually unexclusive ionotropic and metabotropic mechanisms. However, other than one report on the contribution of astrocyte-located NMDARs to astrocyte-dependent modulation of presynaptic strength in the hippocampus, there is no sound evidence for the significant role of astrocytic NMDARs in astrocytic-neuronal interaction in neurotransmission, as yet. Durable exposure of astrocytic and neuronal co-cultures to NMDA has been reported to upregulate astrocytic synthesis of glutathione, and in this way to increase the antioxidative capacity of neurons. On the other hand, overexposure to NMDA decreases, by an as yet unknown mechanism, the ability of cultured astrocytes to express glutamine synthetase (GS), aquaporin-4 (AQP4), and the inward rectifying potassium channel Kir4.1, the three astroglia-specific proteins critical for homeostatic function of astrocytes. The beneficial or detrimental effects of astrocytic NMDAR stimulation revealed in the in vitro studies remain to be proven in the in vivo setting.
Protective Smell of Hydrogen Sulfide and Polysulfide in Cisplatin-Induced Nephrotoxicity
Authors: Cao Xu , Zhang Wencan , Moore Philip K. , Bian Jinsong
Published: January 2019

Though historically known as a toxic gas, hydrogen sulfide (H2S) has displayed a new face as the third endogenous gaseous signaling molecule after nitric oxide (NO) and carbon monoxide (CO). Here in this review, we survey the role and therapeutic potential of H2S in cisplatin-induced nephrotoxicity. Specifically, reduction of H2S by cystathionine γ-lyase (CSE) downregulation upon cisplatin treatment may contribute to cisplatin-induced renal cell injury, possibly by augmentation of endogenous reactive oxygen species (ROS) production, while H2S donation may prevent subsequent renal dysfunction by inhibiting NADPH oxidase activation. Intriguingly, H2S slow-releasing compound GYY4137 seems to increase the anticancer activity of cisplatin, at least in several cancer cell lines, and this is probably due to its own anticancer effect. However, the efficacy of H2S donors in tumor-bearing animals remains to be tested in terms of renal protection and cancer inhibition after receiving cisplatin. Furthermore, accumulative evidence regarding usage of polysulfide, a novel H2S derived molecule, in the therapy of cisplatin-induced nephrotoxicity, was also summarized.
Redifferentiation of Articular Chondrocytes by Hyperacute Serum and Platelet Rich Plasma in Collagen Type I Hydrogels
Authors: Jeyakumar Vivek , Niculescu-Morzsa Eugenia , Bauer Christoph , Lacza Zsombor , Nehrer Stefan
Published: January 2019

Matrix-assisted autologous chondrocyte transplantation (MACT) for focal articular cartilage defects often fails to produce adequate cartilage-specific extracellular matrix in vitro and upon transplantation results in fibrocartilage due to dedifferentiation during cell expansion. This study aimed to redifferentiate the chondrocytes through supplementation of blood-products, such as hyperacute serum (HAS) and platelet-rich plasma (PRP) in vitro. Dedifferentiated monolayer chondrocytes embedded onto collagen type I hydrogels were redifferentiated through supplementation of 10% HAS or 10% PRP for 14 days in vitro under normoxia (20% O2) and hypoxia (4% O2). Cell proliferation was increased by supplementing HAS for 14 days (p < 0.05) or by interchanging from HAS to PRP during Days 7–14 (p < 0.05). Sulfated glycosaminoglycan (sGAG) content was deposited under both HAS, and PRP for 14 days and an interchange during Days 7–14 depleted the sGAG content to a certain extent. PRP enhanced the gene expression of anabolic markers COL2A1 and SOX9 (p < 0.05), whereas HAS enhanced COL1A1 production. An interchange led to reduction of COL1A1 and COL2A1 expression marked by increased MMP13 expression (p < 0.05). Chondrocytes secreted less IL-6 and more PDGF-BB under PRP for 14 days (p < 0.0.5). Hypoxia enhanced TGF-β1 and BMP-2 release in both HAS and PRP. Our study demonstrates a new approach for chondrocyte redifferentiation.
Natural Killer Cells and Current Applications of Chimeric Antigen Receptor-Modified NK-92 Cells in Tumor Immunotherapy
Authors: Zhang Jianguang , Zheng Huifang , Diao Yong
Published: January 2019

Natural killer (NK) cells are innate immune cells that can be activated rapidly to target abnormal and virus-infected cells without prior sensitization. With significant advancements in cell biology technologies, many NK cell lines have been established. Among these cell lines, NK-92 cells are not only the most widely used but have also been approved for clinical applications. Additionally, chimeric antigen receptor-modified NK-92 cells (CAR-NK-92 cells) have shown strong antitumor effects. In this review, we summarize established human NK cell lines and their biological characteristics, and highlight the applications of NK-92 cells and CAR-NK-92 cells in tumor immunotherapy.
Silkworm Storage Protein 1 Inhibits Autophagy-Mediated Apoptosis
Authors: Kang Su Jin , Rhee Won Jong
Published: January 2019

Autophagy is a natural physiological process, and it induces the lysosomal degradation of intracellular components in response to environmental stresses, including nutrient starvation. Although an adequate autophagy level helps in cell survival, excessive autophagy triggered by stress such as starvation leads to autophagy-mediated apoptosis. Chinese hamster ovary (CHO) cells are widely used for producing biopharmaceuticals, including monoclonal antibodies. However, apoptosis induced by high stress levels, including nutrient deficiency, is a major problem in cell cultures grown in bioreactors, which should be overcome. Therefore, it is necessary to develop a method for suppressing excessive autophagy and for maintaining an appropriate autophagy level in cells. Therefore, we investigated the effect of silkworm storage protein 1 (SP1), an antiapoptotic protein, on autophagy-mediated apoptosis. SP1-expressing CHO cells were generated to assess the effect and molecular mechanism of SP1 in suppressing autophagy. These cells were cultured under starvation conditions by treatment with Earle’s balanced salt solution (EBSS) to induce autophagy. We observed that SP1 significantly inhibited autophagy-mediated apoptosis by suppressing caspase-3 activation and reactive oxygen species generation. In addition, SP1 suppressed EBSS-induced conversion of LC3-I to LC3-II and the expression of autophagy-related protein 7. Notably, basal Beclin-1 level was significantly low in the SP1-expressing cells, indicating that SP1 regulated upstream events in the autophagy pathway. Together, these findings suggest that SP1 offers a new strategy for overcoming severe autophagy-mediated apoptosis in mammalian cells, and it can be used widely in biopharmaceutical production.
Identifying a Medical Department Based on Unstructured Data: A Big Data Application in Healthcare
Authors: Bansal Veena , Poddar Abhishek , Ghosh-Roy R.
Published: January 2019

Health is an individual’s most precious asset and healthcare is one of the vehicles for preserving it. The Indian government’s spend on healthcare system is relatively low (1.2% of GDP). Consequently, Secondary and Tertiary government healthcare centers in India (that are presumed to be of above average ratings) are always crowded. In Tertiary healthcare centers, like the All India Institute of Medical Science (AIIMS), patients are often unable to articulate their problems correctly to the healthcare center’s reception staff, so that these patients to be directed to the correct healthcare department. In this paper, we propose a system that will scan prescriptions, referral letters and medical diagnostic reports of a patient, process the input using OCR (Optical Character Recognition) engines, coupled with image processing tools, to direct the patient to the most relevant department. We have implemented and tested parts of this system wherein a patient enters his symptoms and/or provisional diagnosis; the system suggests a department based on this user input. Our system suggests the correct department 70.19% of the time. On further investigation, we found that one particular department of the hospital was over-represented. We eliminated the department from the data and performance of the system improved to 92.7%. Our system presently makes its suggestions using random forest algorithm that has been trained using two information repositories-symptoms and disease data, functional description of each medical department. It is our informed assumption that, once we have incorporated medicine information and diagnostics imaging data to train the system; and the complete medical history of the patient, performance of the system will improve further.
A Study of Minimum Quantity Lubrication (MQL) by Nanofluids in Orbital Drilling and Tribological Testing
Authors: Mosleh Mohsen , Shirvani Khosro A. , Smith Sonya T. , Belk John H. , Lipczynski Gary
Published: January 2019

In minimum quantity lubrication (MQL), an aerosol containing a minimum amount of the cutting fluid is delivered to the tool/workpiece interface during the metal cutting operation. The fluid lubrication by the fluid and the cooling by the compressed air in the aerosol improves the cutting process, while the low consumption rate in MQL provides less cleanup and reduces the associated cost. In this paper, molybdenum disulfide (MoS2) and hexagonal boron nitride (hBN) nanoparticles were added to the aerosol for providing a third functionality to the MQL, which is solid lubrication at the interface. Both orbital drilling and tribological testing using a four-ball tester were studied to examine the effectiveness of solid lubrication in MQL. In orbital drilling of titanium with tungsten carbide tools, MQL with nanofluids containing MoS2 nanoparticles resulted in less transfer film buildup on the tool. In four-ball testing, MQL with nanofluids with MoS2 and hBN nanoparticles yielded lower surface temperatures and less variation of frictional torques in titanium.
Acknowledgement to Reviewers of Languages in 2018
Authors:   Languages Editorial Office
Published: January 2019

Rigorous peer-review is the corner-stone of high-quality academic publishing [...]
Lamellar-like Electrospun Mesoporous Ti-Al-O Nanofibers
Authors: Elishav Oren , Poliak Liz , Naamat Iris , Beilin Vadim , Shter Gennady E. , Grader Gideon S.
Published: January 2019

Ceramic oxides nanofibers are promising materials as catalysts, electrodes and functional materials. In this report, a unique lamellar-like mesoporous structure was realized for the first time in a new system based on titania and alumina. The final structure was found to be highly dependent on the process conditions which are outlined herein. In view of the similar architecture we recently obtained with Fe-Al-O fibers, the pore formation mechanism we outline herein is general and is applicable to additional systems.
Epitaxial Growth of Orthorhombic GaFeO3 Thin Films on SrTiO3 (111) Substrates by Simple Sol-Gel Method
Authors: Zhang Minghui , Yasui Shintaro , Katayama Tsukasa , Rao Badari Narayana , Wen Haiqin , Pan Xiuhong , Tang Meibo , Ai Fei , Itoh Mitsuru
Published: January 2019

A Sol-gel method assisted with spin-coating has been successfully used to grow orthorhombic GaFeO3 epitaxial films on SrTiO3 (111) substrates for the first time. The film with Pna21 crystal structure has been grown along the c-axis. The rocking curve of (004) reflection shows that the Full-Width at Half-Maximum (FWHM) value could be determined to be 0.230°, indicating good single crystallinity and high quality. X-ray Φ scan reveals a three-fold symmetry of the substrate and a six-fold symmetry of the film, respectively. The in-plane domains rotate 60° from each other in the film. Uniform film with dense structure, columnar grains with similar grain size was obtained. The thickness of the film was evaluated to be ~170 nm. The roughness value (RMS) measured by AFM was 4.5 nm, revealing a flat film. The in-plane Magnetization versus Magnetic field (M-H) curve at 5 K performs a typical ferri- or ferromagnetic hysteresis loop with a saturated magnetization (Ms) value of 136 emu/cm3. The Curie temperature could be determined to be 174 K. Compared to Pulsed Laser Deposition (PLD), the sol-gel method can prepare large area films with low cost. These new films show promising applications in multiferroic devices.
Numerical Modeling of Earthquake-Damaged Circular Bridge Columns Repaired Using Combination of Near-Surface-Mounted BFRP Bars with External BFRP Sheets Jacketing
Authors: Zeng Xing-Gui , Jiang Shao-Fei , Xu Xin-Cheng , Huang Hai-Sheng
Published: January 2019

This paper reports the numerical simulation of earthquake-damaged circular columns repaired with the combination of near-surface-mounted (NSM) basalt fiber reinforced polymer (BFRP) bars with external BFRP sheets jacketing at quasi-static loading. The numerical modeling was carried out with the nonlinear OpenSees software platform by using the BeamWithHinges element. In the simulations, the effect of the previous earthquake damage on the behavior of the repaired columns was taken into account, and a simple and effective material damage-accumulation model is proposed to modify the constitutive of materials in the unrepaired regions of the repaired columns. The developed numerical models were validated by comparing their quasi-static findings with those obtained from a previous experimental program, and a good agreement can be observed. Furthermore, the efficiency of the repair technique used in tests is evaluated via the developed numerical model.
Process-Induced Stress and Deformation of Variable-Stiffness Composite Cylinders During Curing
Authors: Zhang Guiming , Wang Jihui , Ni Aiqing
Published: January 2019

Predicting and controlling process-induced deformation of composites during cure can play a significant role in ensuring the accuracy of manufacture and assembly of composite structures. In this paper the parametric investigation on the process-induced stress and deformation of variable-stiffness composite cylinders was presented. The Kamal model was used to simulate the cure kinetic for carbon/epoxy prepreg. A cure hardening instantaneously linear elastic (CHILE) constitutive model was adopted to determine the modulus of matrix resin. Self-consistent micro-mechanical models were employed to represent the mechanical properties and behaviors of the lamina. The three-dimensional model of a variable-stiffness composite cylinder was established using a linear fiber angle variation. The influence of the inner radius, the fiber end angle and the thickness on the stress and deformation of the variable-stiffness cylinder was evaluated using ABAQUS. The results show that the maximum stress increases with increases of the inner radius, the fiber end angle and the thickness. The inner radius of the cylinder have little effect on deformation, the deformation increases as the fiber end angle and the thickness increases. The present model and method can provide a useful tool for prediction of variable-stiffness composite cylinders.
Forward and Inverse Dynamics of a Unicycle-Like Mobile Robot
Authors: Pappalardo Carmine Maria , Guida Domenico
Published: January 2019

In this research work, a new method for solving forward and inverse dynamic problems of mechanical systems having an underactuated structure and subjected to holonomic and/or nonholonomic constraints is developed. The method devised in this paper is based on the combination of the Udwadia-Kalaba Equations with the Underactuation Equivalence Principle. First, an analytical method based on the Udwadia-Kalaba Equations is employed in the paper for handling dynamic and control problems of nonlinear nonholonomic mechanical systems in the same computational framework. Subsequently, the Underactuation Equivalence Principle is used for extending the capabilities of the Udwadia-Kalaba Equations from fully actuated mechanical systems to underactuated mechanical systems. The Underactuation Equivalence Principle represents an efficient method recently developed in the field of classical mechanics. The Underactuation Equivalence Principle is used in this paper for mathematically formalizing the underactuation property of a mechanical system considering a particular set of nonholonomic algebraic constraints defined at the acceleration level. On the other hand, in this study, the Udwadia-Kalaba Equations are analytically reformulated in a mathematical form suitable for treating inverse dynamic problems. By doing so, the Udwadia-Kalaba Equations are employed in conjunction with the Underactuation Equivalence Principle for developing a nonlinear control method based on an inverse dynamic approach. As shown in detail in this investigation, the proposed method can be used for analytically solving in an explicit manner the forward and inverse dynamic problems of several nonholonomic mechanical systems. In particular, the tracking control of the unicycle-like mobile robot is considered in this investigation as a benchmark example. Numerical experiments on the dynamic model of the unicycle-like mobile robot confirm the effectiveness of the nonlinear dynamic and control approaches developed in this work.
Photo-Cured Glycol Chitosan Hydrogel for Ovarian Cancer Drug Delivery
Authors: Hyun Hoon , Park Min Ho , Jo Gayoung , Kim So Yeon , Chun Heung Jae , Yang Dae Hyeok
Published: January 2019

In this study, we prepared an injectable drug delivery depot system based on a visible light-cured glycol chitosan (GC) hydrogel containing paclitaxel (PTX)-complexed beta-cyclodextrin (β-CD) (GC/CD/PTX) for ovarian cancer (OC) therapy using a tumor-bearing mouse model. The hydrogel depot system had a 23.8 Pa of storage modulus at 100 rad/s after visible light irradiation for 10 s. In addition, GC was swollen as a function of time. However, GC had no degradation with the time change. Eventually, the swollen GC matrix affected the releases of PTX and CD/PTX. GC/PTX and GC/CD/PTX exhibited a controlled release of PTX for 7 days. In addition, GC/CD/PTX had a rapid PTX release for 7 days due to improved water solubility of PTX through CD/PTX complex. In vitro cell viability tests showed that GC/CD/PTX had a lower cell viability percentage than the free PTX solution and GC/PTX. Additionally, GC/CD/PTX resulted in a superior antitumor effect against OC. Consequently, we suggest that the GC/CD system might have clinical potential for OC therapy by improving the water solubility of PTX, as PTX is included into the cavity of β-CD.
Inhibition of Adipogenesis by Diphlorethohydroxycarmalol (DPHC) through AMPK Activation in Adipocytes
Authors: Kang Min-Cheol , Ding Yuling , Kim Hyun-Soo , Jeon You-Jin , Lee Seung-Hong
Published: January 2019

The purpose of this study was to investigate the antiobesity effect and the mechanism of action of diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae in 3T3-L1 cells. The antiobesity effects were examined by evaluating intracellular fat accumulation in Oil Red O-stained adipocytes. Based on the results, DPHC dose-dependently inhibited the lipid accumulation in 3T3-L1 adipocytes. DPHC significantly inhibited adipocyte-specific proteins such as SREBP-1c, PPARγ, C/EBP α, and adiponectin, as well as adipogenic enzymes, including perilipin, FAS, FABP4, and leptin in adipocytes. These results indicated that DPHC primarily acts by regulating adipogenic-specific proteins through inhibiting fat accumulation and fatty acid synthesis in adipocytes. DPHC treatment significantly increased both AMPK and ACC phosphorylation in adipocytes. These results indicate that DPHC inhibits the fat accumulation by activating AMPK and ACC in 3T3-L1 cells. Taken together, these results suggest that DPHC can be used as a potential therapeutic agent against obesity.
Citrinin Monomer and Dimer Derivatives with Antibacterial and Cytotoxic Activities Isolated from the Deep Sea-Derived Fungus Penicillium citrinum NLG-S01-P1
Authors: Wang Weiyi , Liao Yanyan , Zhang Beibei , Gao Maolin , Ke Wenqian , Li Fang , Shao Zongze
Published: January 2019

Two previously unreported citrinin dimer derivatives, penicitol D (1) and 1-epi-citrinin H1 (2), were isolated from the culture of a deep sea-derived fungus Penicillium citrinum NLG-S01-P1, together with 11 biogenetic related compounds (3–13). A plausible biogenetic pathway for compounds 2–4 was proposed. Their structures, including absolute configurations, were established through analysis of extensive spectroscopic data and time-dependent density functional theory (TD-DFT) ECD calculations. Compounds 1 and 2 showed antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA). Compounds 5 and 10 displayed relatively stronger activities than the other compounds against Vibrio vulnificus and Vibrio campbellii. Compound 1 showed the most potent cytotoxic activity towards the HeLa cell.
Novel Antibacterial Peptides Isolated from the Maillard Reaction Products of Half-Fin Anchovy (Setipinna taty) Hydrolysates/Glucose and Their Mode of Action in Escherichia Coli
Authors: Wang Jiaxing , Wei Rongbian , Song Ru
Published: January 2019

The Maillard reaction products (MRPs) of half-fin anchovy hydrolysates and glucose, named as HAHp(9.0)-G MRPs, were fractionated by size exclusion chromatography into three major fractions (F1–F3). F2, which demonstrated the strongest antibacterial activity against Escherichia coli (E. coli) and showed self-production of hydrogen peroxide (H2O2), was extracted by solid phase extraction. The hydrophobic extract of F2 was further isolated by reverse phase-high performance liquid chromatography into sub-fractions HE-F2-1 and HE-F2-2. Nine peptides were identified from HE-F2-1, and two peptides from HE-F2-2 using liquid chromatography-electrospray ionization/multi-stage mass spectrometry. Three peptides, FEDQLR (HGM-Hp1), ALERTF (HGM-Hp2), and RHPEYAVSVLLR (HGM-Hp3), with net charges of −1, 0, and +1, respectively, were synthesized. The minimal inhibitory concentration of these synthetic peptides was 2 mg/mL against E. coli. Once incubated with logarithmic growth phase of E. coli, HGM-Hp1 and HGM-Hp2 induced significant increases of both extracellular and intracellular H2O2 formation. However, HGM-Hp3 only dramatically enhanced intracellular H2O2 production in E. coli. The increased potassium ions in E. coli suspension after addition of HGM-Hp1 or HGM-Hp2 indicated the destruction of cell integrity via irreversible membrane damage. It is the first report of hydrolysates MRPs-derived peptides that might perform the antibacterial activity via inducing intracellular H2O2 production.
Marine Bacterial Polysaccharide EPS11 Inhibits Cancer Cell Growth and Metastasis via Blocking Cell Adhesion and Attenuating Filiform Structure Formation
Authors: Wang Ju , Liu Ge , Ma Weiping , Lu Zhongxia , Sun Chaomin
Published: January 2019

Our previous results suggested that EPS11, a novel marine bacterial polysaccharide, might be a potential drug candidate for human non-small cell lung carcinoma treatment. In this study, we further investigate the anticancer mechanisms against liver cancer and the anti-metastatic effects in vivo of EPS11. Firstly, we found that EPS11 exerts cytotoxic effects via blocking cell adhesion and destroying filiform structure formation in Huh7.5 cells. Moreover, mass spectrometry-based proteomic analysis of EPS11-treated Huh7.5 cells revealed that expression of many adhesion-related proteins was significantly changed. It is noteworthy that the expression of CD99, a key factor related to cell adhesion, migration and cell death, is remarkably down-regulated after EPS11 treatment. Importantly, over-expression of CD99 partly rescues cell death rate, and improves cell adhesion and migration ability in Huh7.5 treated by EPS11. Thus, we propose that CD99 is a potential action target of EPS11, inhibiting cancer cell proliferation, adhesion and migration. Notably, administration of EPS11 simultaneously with tumor induction evidently reduces tumor nodule formation in the lungs, which strongly indicates that EPS11 has anti-metastatic effects in vivo. Taken together, our results suggest that EPS11 inhibits liver cancer cell growth via blocking cell adhesion and attenuating filiform structure formation, and has potential as an anti-cancer drug, targeting metastasis of cancer cells, in the future.
UVA and UVB Photoprotective Capabilities of Topical Formulations Containing Mycosporine-like Amino Acids (MAAs) through Different Biological Effective Protection Factors (BEPFs)
Authors: de la Coba Francisca , Aguilera José , Korbee Nathalie , de Gálvez María Victoria , Herrera-Ceballos Enrique , Álvarez-Gómez Félix , Figueroa Félix L.
Published: January 2019

The safety and stability of synthetic UV-filters and the procedures for evaluating the photoprotective capability of commercial sunscreens are under continuous review. The influence of pH and temperature stressors on the stability of certain Mycosporine-like amino acids (MAAs) isolated at high purity levels was examined. MAAs were highly stable at room temperature during 24 h at pH 4.5–8.5. At 50 °C, MAAs showed instability at pH 10.5 while at 85 °C, progressive disappearances were observed for MAAs through the studied pH range. In alkaline conditions, their degradation was much faster. Mycosporine-serinol and porphyra-334 (+shinorine) were the most stable MAAs under the conditions tested. They were included in four cosmetically stable topical sunscreens, of which the Sun Protection Factor (SPF) and other Biological Effective Protection Factors (BEPFs) were calculated. The formulation containing these MAAs showed similar SPF and UVB-BEPFs values as those of the reference sunscreen, composed of synthetic UV absorbing filters in similar percentages, while UVA-BEPFs values were slightly lower. Current in vitro data strongly suggest that MAAs, as natural and safe UV-absorbing and antioxidant compounds, have high potential for protection against the diverse harmful effects of solar UV radiation. In addition, novel complementary in vitro tests for evaluation of commercial sunscreens efficacy are proposed.
Slot-Die Coating of Double Polymer Layers for the Fabrication of Organic Light Emitting Diodes
Authors: C Amruth , Colella Marco , Griffin Jonathan , Kingsley James , Scarratt Nicholas , Luszczynska Beata , Ulanski Jacek
Published: January 2019

This study presents the slot-die coating process of two layers of organic materials for the fabrication of organic light emitting diodes (OLEDs). Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), which is commonly used in OLEDs and in organic photovoltaic devices as the hole injection layer (HIL), has been deposited via slot-die coating. Uniform films of PEDOT:PSS were obtained after optimizing the slot-die processing parameters: substrate temperature, coating speed, and ink flow rate. The film quality was examined using optical microscopy, profilometry, and atomic force microscopy. Further, poly(9,9-dioctylfluorene) (F8) and poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT), a well know polymer blend F8:F8BT, which is used as an emissive layer in OLEDs, has been slot-die coated. The optoelectronic properties of the slot-die coated F8:F8BT films were examined by means of photoluminescence (PL) and electroluminescence (EL) studies. The fabricated OLEDs, consisting of slot-die coated PEDOT:PSS and F8:F8BT films, were characterized to record the brightness and current efficiency.
Spray-On Liquid-Metal Electrodes for Graphene Field-Effect Transistors
Authors: Melcher Jordan L. , Elassy Kareem S. , Ordonez Richard C. , Hayashi Cody , Ohta Aaron T. , Garmire David
Published: January 2019

Advancements in flexible circuit interconnects are critical for widespread adoption of flexible electronics. Non-toxic liquid-metals offer a viable solution for flexible electrodes due to deformability and low bulk resistivity. However, fabrication processes utilizing liquid-metals suffer from high complexity, low throughput, and significant production cost. Our team utilized an inexpensive spray-on stencil technique to deposit liquid-metal Galinstan electrodes in top-gated graphene field-effect transistors (GFETs). The electrode stencils were patterned using an automated vinyl cutter and positioned directly onto chemical vapor deposition (CVD) graphene transferred to polyethylene terephthalate (PET) substrates. Our spray-on method exhibited a throughput of 28 transistors in under five minutes on the same graphene sample, with a 96% yield for all devices down to a channel length of 50 μm. The fabricated transistors possess hole and electron mobilities of 663.5 cm2/(V·s) and 689.9 cm2/(V·s), respectively, and support a simple and effective method of developing high-yield flexible electronics.
Bacterial Concentration Detection using a PCB-based Contactless Conductivity Sensor
Authors: Zhang Xiao-Yan , Li Zhe-Yu , Zhang Yu , Zang Xiao-Qian , Ueno Kosei , Misawa Hiroaki , Sun Kai
Published: January 2019

Capacitively coupled contactless conductivity detection (C4D) is an improved approach to avoid the problems of labor-intensive, time-consuming and insufficient accuracy of plate count as well as the high-cost apparatus of flow cytometry (FCM) in bacterial counting. This article describes a novel electrode-integrated printed-circuit-board (PCB)-based C4D device, which supports the simple and safe exchange of capillaries and improves the sensitivity and repeatability of the contactless detection. Furthermore, no syringe pump is needed in the detection, it reduces the system size, and, more importantly, avoids the effect on the bacteria due to high pressure. The recovered bacteria after C4D detection at excitation of 25 Vpp and 60–120 kHz were analyzed by flow cytometry, and a survival rate higher than 96% was given. It was verified that C4D detection did not influence the bacterial viability. Moreover, bacteria concentrations from 106 cells/mL to 108 cells/mL were measured in a linear range, and relative standard deviation (RSD) is below 0.2%. In addition, the effects on bacteria and C4D from background solutions were discussed. In contrast to common methods used in most laboratories, this method may provide a simple solution to in situ detection of bacterial cultures.
Acknowledgement to Reviewers of Nutrients in 2018
Authors:   Nutrients Editorial Office
Published: January 2019

Rigorous peer-review is the corner-stone of high-quality academic publishing [...]
The Psychology of Nutrition with Advancing Age: Focus on Food Neophobia
Authors: van den Heuvel Emmy , Newbury Annie , Appleton Katherine M.
Published: January 2019

Many factors impact on eating behaviour and nutritional status in older adults. Strategies can be suggested to combat the impact of these factors, including the development of novel food products, but food neophobia (“the reluctance to eat and/or avoidance of novel foods”) may be a barrier to the acceptance of these foods/products. This work aimed to investigate associations between food neophobia, physical disadvantage, and demographic characteristics in adults over 55 years old. Cross-sectional data from 377 older adults was analysed for relationships between food neophobia scores and physical disadvantage (denture wearing, help with food shopping and/or preparing, and risk of sarcopenia), controlling for age group, gender, living status, education, and employment level. Initial analyses demonstrated higher food neophobia scores in association with denture wearing (Beta = 0.186, p = 0.001). However, when demographic characteristics were also considered, food neophobia scores were no longer related to denture wearing (Beta = 0.069, p = 0.226) but instead were related to a higher age, living alone, and a shorter education (smallest Beta = −0.104, p = 0.048). Food neophobia may thus act as a barrier to the consumption of novel foods/products in those who are of higher age, are living alone, and have a shorter education.
Beneficial Effects of an Aged Black Garlic Extract in the Metabolic and Vascular Alterations Induced by a High Fat/Sucrose Diet in Male Rats
Authors: Amor Sara , González-Hedström Daniel , Martín-Carro Beatriz , Inarejos-García Antonio , Almodóvar Paula , Prodanov Marin , García-Villalón Angel , Granado Miriam
Published: January 2019

Aged black garlic (ABG) is a functional food with antioxidant and anti-inflammatory properties. Recent studies also report its beneficial metabolic effects in a context of obesity or diabetes, although the mechanisms involved are poorly understood. The aim of this work was to analyze the effects of an ABG extract in the vascular and metabolic alterations induced by a high-fat/sucrose diet in rats. For this purpose, male Sprague–Dawley rats were fed either a standard chow (controls; n = 12) or a high-fat/sucrose diet (HFD; n = 24) for 16 weeks. From week 8 on, half of the HFD rats were treated with a commercial ABG extract concentrated in S-allyl cysteine and melanoidins (ABG10+®; 250 mg/kg daily by gavage; 5 mL/kg). ABG10+®-treated rats showed lower mean caloric intake, body weight, triglycerides, low density lipoprotein cholesterol (LDL-c), insulin and leptin serum concentrations and higher high density lipoprotein cholesterol (HDL-c) and adiponectin serum concentrations than non-treated rats. In the hypothalamus, ABG10+® treatment induced an increase in the gene expression of proopiomelanocortin (POMC) and a decrease in leptin receptor (ObR) mRNA levels. No significant changes were found in visceral adipose tissue except for an overexpression of β3-adrenergic receptor (β3-ADR) in ABG-treated rats. In subcutaneous adipose tissue, ABG10+® treatment decreased adipose weight and downregulated the gene expression of PPAR-γ, LPL, ObR and HSL. In brown adipose tissue, an overexpression of InsR, GLUT-4, UCP-1 and β3-ADR in ABG10+®-treated rats was found, whereas PPAR-γ mRNA levels were significantly decreased. Regarding vascular function, ABG10+® treatment attenuated the obesity-induced vasoconstriction in response to potassium chloride both in presence/absence of perivascular adipose tissue (PVAT). On the contrary, aorta segments from ABG-treated rats showed and improved relaxation in response to acetylcholine only when PVAT was present, with this fact possible being related to the decreased gene expression of proinflammatory cytokines in this tissue. In conclusion, ABG10+® administration partially improves the metabolic and vascular alterations induced by a high-fat/high-sucrose diet in rats through modifications in the gene expression of proteins and neuropeptides involved in inflammation, fat metabolism and food intake regulation. Further studies are required to assess the bioavailability of ABG between rats and humans.
Optimization of the Automated Synthesis of [11C]mHED—Administered and Apparent Molar Activities
Authors: Vraka Chrysoula , Pichler Verena , Berroterán-Infante Neydher , Wollenweber Tim , Pillinger Anna , Hohensinner Maximilian , Fetty Lukas , Beitzke Dietrich , Li Xiang , Philippe Cecile , Pallitsch Katharina , Mitterhauser Markus , Hacker Marcus , Wadsak Wolfgang
Published: January 2019

The tracer [11C]meta-Hydroxyephedrine ([11C]mHED) is one of the most applied PET tracers for cardiac imaging, whose radiosynthesis was already reported in 1990. While not stated in the literature, separation difficulties and an adequate formulation of the product are well known challenges in its production. Furthermore, the precursor (metaraminol) is also a substrate for the norepinephrine transporter, and can therefore affect the image quality. This study aims at optimizing the synthetic process of [11C]mHED and investigating the effect of the apparent molar activity (sum of mHED and metaraminol) in patients and animals. The main optimization was the improved separation through reverse phase-HPLC by a step gradient and subsequent retention of the product on a weakly-cationic ion exchange cartridge. The µPET/µCT was conducted in ten rats (ischemic model) and the apparent molar activity was correlated to the VOI- and SUV-ratio of the myocardium/intra-ventricular blood pool. Moreover, nine long-term heart transplanted and five Morbus Fabry patients underwent PET and MRI imaging for detection of changes in the sympathetic innervation. In summary, the fully-automated synthesis and optimized purification method of [11C]mHED is easily applicable and reproducible. Moreover, it was shown that the administered apparent molar activities had a negligible effect on the imaging quality.