bluuebunny/crossref_metadata_2025 huggingface dataset:
Adsorption Performance of Physically Activated Biochars for Postcombustion CO2 Capture from Dry and Humid Flue Gas
Authors: Manyà Joan J. , García-Morcate David , González Belén
Published: January 2020

In the present study, the performance of four biomass-derived physically activated biochars for dynamic CO2 capture was assessed. Biochars were first produced from vine shoots and wheat straw pellets through slow pyrolysis (at pressures of 0.1 and 0.5 MPa) and then activated with CO2 (at 0.1 MPa and 800 °C) up to different degrees of burn-off. Cyclic adsorption-desorption measurements were conducted under both dry and humid conditions using a packed-bed of adsorbent at relatively short residence times of the gas phase (12–13 s). The adsorbent prepared from the vine shoots-derived biochar obtained by atmospheric pyrolysis, which showed the most hierarchical pore size distribution, exhibited a good and stable performance under dry conditions and at an adsorption temperature of 50 °C, due to the enhanced CO2 adsorption and desorption rates. However, the presence of relatively high concentrations of water vapor in the feeding gas clearly interfered with the CO2 adsorption mechanism, leading to significantly shorter breakthrough times. In this case, the highest percentages of a used bed were achieved by one of the other activated biochars tested, which was prepared from the wheat straw-derived biochar obtained by pressurized pyrolysis.
Mutual Coupling Reduction of Cross-Dipole Antenna for Base Stations by Using a Neural Network Approach
Authors: Ozdemir Ersin , Akgol Oguzhan , Ozkan Alkurt Fatih , Karaaslan Muharrem , Abdulkarim Yadgar I. , Deng Lianwen
Published: January 2020

In this manuscript, a resonator layer is presented for the purpose of reducing the mutual coupling effect between each antenna element of a cross dipole antenna. In design processes, an artificial neural network approach was used for various resonator designs. In the operating frequency band of 2.2–2.7 GHz, 48 different 6 × 6 resonator layers were created and integrated into the cross dipole antenna to reduce transmission and improve isolation between each antenna elements. Moreover, when training an artificial neural network in the Matlab program, 48 different resonator layers were used with the return losses and transmission values of cross dipole antenna elements. After training process, eight unknown resonator designs were tested and accurate results were obtained. Finally, one of the resonator planes, which was obtained from the artificial neural network, was fabricated and experimentally tested, then an accurate result was obtained. This study provides a good solution, especially for improving isolation in multiport antenna systems, using an artificial neural network approach.
Special Issue Editorial: Nanoparticles in the Atmosphere
Authors: Joutsensaari Jorma
Published: January 2020

The aim of this Special Issue was to gain insight into the current knowledge on nanoparticles in the atmosphere, from laboratory and field measurements to theoretical and modelling studies of nanoparticles from various atmospheric environments [...]
Neuroprotective Effects of Quercetin in Alzheimer’s Disease
Authors: Khan Haroon , Ullah Hammad , Aschner Michael , Cheang Wai San , Akkol Esra Küpeli
Published: January 2020

Quercetin is a flavonoid with notable pharmacological effects and promising therapeutic potential. It is widely distributed among plants and found commonly in daily diets predominantly in fruits and vegetables. Neuroprotection by quercetin has been reported in several in vitro studies. It has been shown to protect neurons from oxidative damage while reducing lipid peroxidation. In addition to its antioxidant properties, it inhibits the fibril formation of amyloid-β proteins, counteracting cell lyses and inflammatory cascade pathways. In this review, we provide a synopsis of the recent literature exploring the relationship between quercetin and cognitive performance in Alzheimer’s disease and its potential as a lead compound in clinical applications.
Epigenetics Analysis and Integrated Analysis of Multiomics Data, Including Epigenetic Data, Using Artificial Intelligence in the Era of Precision Medicine
Authors: Hamamoto Ryuji , Komatsu Masaaki , Takasawa Ken , Asada Ken , Kaneko Syuzo
Published: January 2020

To clarify the mechanisms of diseases, such as cancer, studies analyzing genetic mutations have been actively conducted for a long time, and a large number of achievements have already been reported. Indeed, genomic medicine is considered the core discipline of precision medicine, and currently, the clinical application of cutting-edge genomic medicine aimed at improving the prevention, diagnosis and treatment of a wide range of diseases is promoted. However, although the Human Genome Project was completed in 2003 and large-scale genetic analyses have since been accomplished worldwide with the development of next-generation sequencing (NGS), explaining the mechanism of disease onset only using genetic variation has been recognized as difficult. Meanwhile, the importance of epigenetics, which describes inheritance by mechanisms other than the genomic DNA sequence, has recently attracted attention, and, in particular, many studies have reported the involvement of epigenetic deregulation in human cancer. So far, given that genetic and epigenetic studies tend to be accomplished independently, physiological relationships between genetics and epigenetics in diseases remain almost unknown. Since this situation may be a disadvantage to developing precision medicine, the integrated understanding of genetic variation and epigenetic deregulation appears to be now critical. Importantly, the current progress of artificial intelligence (AI) technologies, such as machine learning and deep learning, is remarkable and enables multimodal analyses of big omics data. In this regard, it is important to develop a platform that can conduct multimodal analysis of medical big data using AI as this may accelerate the realization of precision medicine. In this review, we discuss the importance of genome-wide epigenetic and multiomics analyses using AI in the era of precision medicine.
Intrinsic Disorder-Based Design of Stable Globular Proteins
Authors: Nagibina Galina S. , Glukhova Ksenia A. , Uversky Vladimir N. , Melnik Tatiana N. , Melnik Bogdan S.
Published: January 2020

Directed stabilization of globular proteins via substitution of a minimal number of amino acid residues is one of the most complicated experimental tasks. This work summarizes our research on the effect of amino acid substitutions on the protein stability utilizing the outputs of the analysis of intrinsic disorder predisposition of target proteins. This allowed us to formulate the basis of one of the possible approaches to the stabilization of globular proteins. The idea is quite simple. To stabilize a protein as a whole, one needs to find its "weakest spot" and stabilize it, but the question is how this weak spot can be found in a query protein. Our approach is based on the utilization of the computational tools for the per-residue evaluation of intrinsic disorder predisposition to search for the "weakest spot" of a query protein (i.e., the region(s) with the highest local predisposition for intrinsic disorder). When such "weakest spot" is found, it can be stabilized through a limited number of point mutations by introducing order-promoting residues at hot spots, thereby increasing structural stability of a protein as a whole. Using this approach, we were able to obtain stable mutant forms of several globular proteins, such as Gαo, GFP, ribosome protein L1, and circular permutant of apical domain of GroEL.
The Morphology and Phenotype of Monocyte-Macrophages When Cultured on Bionanofilms Substrates with Different Surface Relief Profiles
Authors: Menzyanova Natalia G. , Pyatina Svetlana A. , Shabanov Alexander V. , Nemtsev Ivan V. , Stolyarov Dmitry P. , Dryganov Dmitry B. , Sakhnov Eugene V. , Shishatskaya Ekaterina I.
Published: January 2020

The effect of surface relief profiles of alkanoate-based bionanofilms to the monocyte-macrophages (MN-MPhs) from peripheral blood of patients with atherosclerosis was studied in vitro. Patients were subjected to coronary stenting. Cell morphology and phenotype (expression of CD antigens, levels of production of marker cytokines) in vitro were analyzed before and after the installation of stents. It was shown, that the mean square roughness (Rq) of the bionanofilms determined the variability of cell morphology, CD antigens spectraand activity of production interleukins-6 and -10. Also, it was revealed, that the “activity” of the surface topography of biopolymer substrates depends on the functional state of MNs, isolated in different time points: Before and after stenting the ratios of cell morphotypes and production of cytokines in MN-MPhs differed significantly.
The Emerging Role of Long Non-Coding RNAs in the Metastasis of Hepatocellular Carcinoma
Authors: Chen Xuejiao , Tang Feng-Ru , Arfuso Frank , Cai Wen-Qi , Ma Zhaowu , Yang Jiyuan , Sethi Gautam
Published: January 2020

Long non-coding RNAs (lncRNAs) play multifaceted roles in modulating gene expression under both physiological and pathological processes. The dysregulation of lncRNAs has been increasingly linked with many human diseases, including a plethora of cancers. Mounting evidence indicates that lncRNAs are aberrantly expressed in hepatocellular carcinoma (HCC) and can regulate HCC progression, as well as metastasis. In this review, we summarize the recent findings on the expanding roles of lncRNAs in modulating various functions of HCC, and elaborate on how can lncRNAs impact HCC metastasis and progression via interacting with chromatin, RNA, and proteins at the epigenetic, transcriptional, and post-transcriptional levels. This mini-review also highlights the current advances regarding the signaling pathways of lncRNAs in HCC metastasis and sheds light on the possible application of lncRNAs for the prevention and treatment of HCC.
An Adrenalectomy Mouse Model Reflecting Clinical Features for Chronic Fatigue Syndrome
Authors: Lee Jin-Seok , Jeon Yoo-Jin , Park Samuel-Young , Son Chang-Gue
Published: January 2020

Chronic fatigue syndrome (CFS) is one of the most intractable diseases and is characterized by severe central fatigue that impairs even daily activity. To date, the pathophysiological mechanisms are uncertain and no therapies exist. Therefore, a proper animal model reflecting the clinical features of CFS is urgently required. We compared two CFS animal models most commonly used, by injection with lipopolysaccharide (LPS from Escherichia coli O111:B4) or polyinosinic: polycytidylic acid (poly I:C), along with bilateral adrenalectomy (ADX) as another possible model. Both LPS- and poly I:C-injected mice dominantly showed depressive behaviors, while ADX led to fatigue-like performances with high pain sensitivity. In brain tissues, LPS injection notably activated microglia and the 5-hydroxytryptamine (HT)1A receptor in the prefrontal cortex and hippocampus. Poly I:C-injection also remarkably activated the 5-HT transporter and 5-HT1A receptor with a reduction in serotonin levels in the brain. ADX particularly activated astrocytes and transforming growth factor beta (TGF-β) 1 in all brain regions. Our results revealed that LPS and poly I:C animal models approximate depressive disorder more closely than CFS. We suggest that ADX is a possible method for establishing a mouse model of CFS reflecting clinical features, especially in neuroendocrine system.
Kinetic, Thermodynamic, and Crystallographic Studies of 2-Triazolylthioacetamides as Verona Integron-Encoded Metallo-β-Lactamase 2 (VIM-2) Inhibitor
Authors: Xiang Yang , Zhang Yue-Juan , Ge Ying , Zhou Yajun , Chen Cheng , Wahlgren Weixiao Yuan , Tan Xiangshi , Chen Xi , Yang Ke-Wu
Published: January 2020

Inhibition of β-lactamases presents a promising strategy to restore the β-lactams antibacterial activity to resistant bacteria. In this work, we found that aromatic carboxyl substituted 2-triazolylthioacetamides 1a–j inhibited VIM-2, exhibiting an IC50 value in the range of 20.6–58.6 μM. The structure-activity relationship study revealed that replacing the aliphatic carboxylic acid with aromatic carboxyl improved the inhibitory activity of 2-triazolylthioacetamides against VIM-2. 1a–j (16 mg/mL) restored the antibacterial activity of cefazolin against E. coli cell expressing VIM-2, resulting in a 4–8-fold reduction in MICs. The isothermal titration calorimetry (ITC) characterization suggested that the primary binding 2-triazolylthioacetamide (1b, 1c, or 1h) to VIM-2 was a combination of entropy and enthalpy contributions. Further, the crystal structure of VIM-2 in complex with 1b was obtained by co-crystallization with a hanging-drop vapour-diffusion method. The crystal structure analysis revealed that 1b bound to two Zn(II) ions of the enzyme active sites, formed H-bound with Asn233 and structure water molecule, and interacted with the hydrophobic pocket of enzyme activity center utilizing hydrophobic moieties; especially for the phenyl of aromatic carboxyl which formed π-π stacking with active residue His263. These studies confirmed that aromatic carboxyl substituted 2-triazolylthioacetamides are the potent VIM-2 inhibitors scaffold and provided help to further optimize 2-triazolylthioacetamides as VIM-2 even or broad-spectrum MβLs inhibitors.
From Translation to Protein Degradation as Mechanisms for Regulating Biological Functions: A Review on the SLRP Family in Skeletal Tissues
Authors: Zappia Jérémie , Joiret Marc , Sanchez Christelle , Lambert Cécile , Geris Liesbet , Muller Marc , Henrotin Yves
Published: January 2020

The extracellular matrix can trigger cellular responses through its composition and structure. Major extracellular matrix components are the proteoglycans, which are composed of a core protein associated with glycosaminoglycans, among which the small leucine-rich proteoglycans (SLRPs) are the largest family. This review highlights how the codon usage pattern can be used to modulate cellular response and discusses the biological impact of post-translational events on SLRPs, including the substitution of glycosaminoglycan moieties, glycosylation, and degradation. These modifications are listed, and their impacts on the biological activities and structural properties of SLRPs are described. We narrowed the topic to skeletal tissues undergoing dynamic remodeling.
Housing Prices in Unregulated Markets: Study on Verticalised Dwellings in Santiago de Chile
Authors: Vergara-Perucich José Francisco , Aguirre-Nuñez Carlos
Published: January 2020

Chile faces a housing affordability crisis, given that most of the population is unable to secure a house. While housing prices between 2008 and 2019 increased by 63.96%, wages only increased by 21.85%. This article presented an analysis of the housing price configuration for the main borough in the country—Santiago. The assessment focused on verticalised housing constructed between 2015 and 2019. The article developed an exploratory study on the price of housing in Santiago to generate a diagnosis to identify the role played by expectations of profitability when configuring price. Based on the information generated, we sought to contribute to the discussion on public policies that advance the development of affordable housing in central boroughs with high urban value, as is the case for Santiago’s borough of Greater Santiago. We hypothesised that profit expectation of real estate developers plays a key role in the housing prices, and an adjustment in the profit ratios might increase the affordability while keeping the housing market above profitable rates. This research addressed the lack of data transparency in the Chilean housing market with archival research, reconstructing costs and earnings from projects based on official registrations of transactions at the borough level. In Chile, the access to investment costs, land values, yields, and house price formation are not publicly available, even though these factors imply that many households are facing severe difficulties in paying for and accessing decent housing.
The Structure Effect on the Activity and Strength of an Industrial Honeycomb Catalyst Derived from Different Ti Sources
Authors: Li Yunjia , Abubakar Abdullahi , Huangfu Lin , Li Changming , Li Jianling , Yu Jian , Gao Shiqiu
Published: January 2020

A new honeycomb production process was proposed with both filter cake (from hydrothermal treatment of metatitanic acid) and industrial titanium dioxide as Ti sources. The strength of the obtained pilot product was comparable with the current industrial honeycomb product from only filter cake, but its denitration (DeNOx) efficiency was elevated up to 15 percentage points. Multiple characterizations revealed the filter cake and industrial titanium dioxide to be composed of primary particles and secondary particles, respectively, and the introduced secondary particles from industrial titanium dioxide resulted in increased specific surface area and pore size/volume, facilitating the exposure of more active sites with improved activity. Moreover, a positive correlation property was found between the honeycomb strength and crystallinity for the samples from different titanium sources. The filter cake with rich hydroxyl groups and weak crystallinity could be fused more easily among these primary particles to have a higher strength than industrial titanium dioxide, and the primary particle of the filter cake could fill the pile pore of industrial titanium dioxide and act as a solid phase binder to acquire good strength for the honeycomb using both the filter cake and titanium dioxide as Ti sources. The improved honeycomb product with good activity and strength may have more widespread application for the purification of low temperature flue gas in industry.
Relationship Between the Pore Structure of Mesoporous Silica Supports and the Activity of Nickel Nanocatalysts in the CO2 Reforming of Methane
Authors: Amin Mohamad Hassan
Published: January 2020

The question remains over the role of the pore structure of the support material on the catalytic behaviour of Ni catalysts during the CO2/dry reforming of methane (DRM). For this reason, a series of mesoporous materials with different pore structures, namely MCM-41, KIT-6, tri-modal porous silica (TMS), SBA-15 and mesostructured cellular foams (MCFs) were synthesised via hydrothermal synthesis methods and further impregnated with 15 wt.% NiO (11.8 wt.% Ni). It was observed that synthesised TMS is a promising catalyst support for DRM as Ni/TMS gave the highest activity and stability among these materials as well as the Ni catalysts supported on classic ordered mesoporous silicates support reported in the literature at the relatively low temperature (700 °C). On the other hand, Ni supported on CMC-41 exhibited the lowest activity among them. To understand the reason for this difference, the physicochemical properties of these materials were characterised in detail. The results show that the thickness of the silica wall and the pore size of the support material play a critical role in the catalytic activity of Ni catalysts in the CO2 reforming of methane.
Hydrogen Production from Ethylene Glycol Aqueous Phase Reforming over Ni–Al Layered Hydrotalcite-Derived Catalysts
Authors: Zhang Jianguang , Xu Ningge
Published: January 2020

By introducing Mg, Cu, Zn, Sn, and Mn into the synthesis processes of Ni and Al based hydrotalcite, Ni–Al layered hydrotalcite-derived catalysts with different metal compositions were prepared. In this paper, the effect of metal composition on the structure of Ni–Al layered hydrotalcite-derived catalysts is investigated, and then catalytic activities of prepared catalysts with different metal compositions on ethylene glycol aqueous-phase reforming are analyzed. The physicochemical properties of the Ni–Al layered hydrotalcite-derived catalysts were characterized by X-ray diffraction (XRD), temperature-programmed reduction (TPR), and nitrogen adsorption–desorption technology. The obtained hydrotalcite-derived catalysts were applied to the process of ethylene glycol aqueous-phase reforming (APR). The XRD results confirmed that the precursors of hydrotalcite-derived catalysts with metal compositions of Ni/Mg/Al, Ni/Cu/Al, Ni/Zn/Al, and Ni/Sn/Al had hydrotalcite crystalloid morphology. During the process of ethylene glycol aqueous phase reforming, all the catalysts showed high conversion of ethylene glycol (>90%), and the optimum hydrogen yield (73.5%) was obtained when using the catalyst with metal composition of Ni/Mg/Al at 225 °C under 2.6 MPa in nitrogen atmosphere for 2.5 h.
Biomimetic Oxidation of Benzofurans with Hydrogen Peroxide Catalyzed by Mn(III) Porphyrins
Authors: Rebelo Susana L. H. , Pires Sónia M. G. , Simões Mário M. Q. , de Castro Baltazar , Neves M. Graça P. M. S. , Medforth Craig J.
Published: January 2020

The modelling of metabolic activation of the benzofuran nucleus is important to obtain eco-sustainable degradation methods and to understand the related mechanisms. The present work reports the catalytic oxidation of benzofuran, 2-methylbenzofuran, and 3-methylbenzofuran by hydrogen peroxide, at room temperature, in the presence of different Mn(III) porphyrins as models of cytochrome P450 enzymes. Conversions above 95% were attained for all the substrates. The key step is the formation of epoxides, which undergo different reaction pathways depending on factors, such as the position of the methyl group and the reaction and work-up conditions used.
The Influence of the Support on the Activity of Mn–Fe Catalysts Used for the Selective Catalytic Reduction of NOx with Ammonia
Authors: López-Hernández Irene , Mengual Jesús , Palomares Antonio Eduardo
Published: January 2020

Mono and bimetallic Mn–Fe catalysts supported on different materials were prepared and their catalytic performance in the NH3–SCR of NOx was investigated. It was shown that Mn and Fe have a synergic effect that enhances the activity at low temperature. Nevertheless, the activity of the bimetallic catalysts depends very much on the support selected. The influence of the support on the catalyst activity has been studied using materials with different textural and acid–base properties. Microporous (BEA-zeolite), mesoporous (SBA15 and MCM41) and bulk (metallic oxides) materials with different acidity have been used as supports for the Mn–Fe catalysts. It has been shown that the activity depends on the acidity of the support and on the surface area. Acid sites are necessary for ammonia adsorption and high surface area produces a better dispersion of the active sites resulting in improved redox properties. The best results have been obtained with the catalysts supported on alumina and on beta zeolite. The first one is the most active at low temperatures but it presents some reversible deactivation in the presence of water. The Mn–Fe catalyst supported on beta zeolite is the most active at temperatures higher than 350 °C, without any deactivation in the presence of water and with a 100% selectivity towards nitrogen.
Doping of Chlorine from a Neoprene Adhesive Enhances Degradation Efficiency of Dyes by Structured TiO2-Coated Photocatalytic Fabrics
Authors: Cao Zhen , Zhang Tingting , Ren Pin , Cao Ding , Lin Yanjun , Wang Liren , Zhang Bing , Xiang Xu
Published: January 2020

We demonstrate that using neoprene as a binder during the fabrication of TiO2-coated fabrics enhances the rates of photodegradation of dyes by the fabrics. The neoprene binder simultaneously modifies the surface of the TiO2 particles with Cl and dopes the TiO2 with Cl, without requiring high temperatures or other harsh laboratory treatments. The adsorption of chlorine on the surface and doping of the lattice with chlorine were confirmed by X-ray photoelectron spectroscopy. The chloride ions adsorbed onto the TiO2 surface introduces a negative surface charge that enhances electrostatic adsorption of cationic dyes, and greatly improves the self-sensitizing degradation performance of the dyes. Chloride ions replace lattice oxygen atoms in TiO2, inducing lattice oxygen vacancies, that reduce the apparent band gap of the TiO2 particles, enhancing its absorption of visible light, and further increasing the photocatalytic activity of the composite-coated fabric. The degradation rates of RhB and MB over 50 min were 95.2% and 96.0%, respectively. The degradation rate for MO reached 95.4% after 180 min. We also show that •OH and •O2− are active agents in the dye-degradation mechanism. Moreover, the photocatalytic performance of the composite-coated fabric was unchanged after eight cycles of photocatalytic degradation of RhB, demonstrating that the photocatalyst-coated fabrics was highly recyclable.
Promoting Effect of the Core-Shell Structure of MnO2@TiO2 Nanorods on SO2 Resistance in Hg0 Removal Process
Authors: Zhang Xiaopeng , Han Xiangkai , Li Chengfeng , Song Xinxin , Zhu Hongda , Bao Junjiang , Zhang Ning , He Gaohong
Published: January 2020

Sorbent of αMnO2 nanorods coating TiO2 shell (denoted as αMnO2-NR@TiO2) was prepared to investigate the elemental mercury (Hg0) removal performance in the presence of SO2. Due the core-shell structure, αMnO2-NR@TiO2 has a better SO2 resistance when compared to αMnO2 nanorods (denoted as αMnO2-NR). Kinetic studies have shown that both the sorption rates of αMnO2-NR and αMnO2-NR@TiO2, which can be described by pseudo second-order models and SO2 treatment, did not change the kinetic models for both the two catalysts. In contrast, X-ray photoelectron spectroscopy (XPS) results showed that, after reaction in the presence of SO2, S concentration on αMnO2-NR@TiO2 surface is lower than on αMnO2-NR surface, which demonstrated that TiO2 shell could effectively inhibit the SO2 diffusion onto MnO2 surface. Thermogravimetry-differential thermosgravimetry (TG-DTG) results further pointed that SO2 mainly react with TiO2 forming Ti(SO4)O in αMnO2-NR@TiO2, which will protect Mn from being deactivated by SO2. These results were the reason for the better SO2 resistance of αMnO2-NR@TiO2.
Octyl Gallate Induces Pancreatic Ductal Adenocarcinoma Cell Apoptosis and Suppresses Endothelial-Mesenchymal Transition-Promoted M2-Macrophages, HSP90α Secretion, and Tumor Growth
Authors: Chua Kee Voon , Fan Chi-Shuan , Chen Chia-Chi , Chen Li-Li , Hsieh Shu-Chen , Huang Tze-Sing
Published: January 2020

Octyl gallate (OG) is a common antioxidant and preservative safely used in food additive and cosmetics. In this study, OG exhibited an activity to induce apoptosis in pancreatic ductal adenocarcinoma (PDAC) cells. It induced BNIP3L level and facilitated physical associations of BNIP3L with Bcl-2 as well as Bcl-XL to set the mitochondrial Bax/Bak channels free for cytochrome c release. In addition, in vivo evaluation also showed that daily oral administration of OG was efficacious to prevent the tumor growth of PDAC cell grafts. Considering PDAC is a desmoplastic tumor consisting of many cancer-associated fibroblasts (CAFs), we further evaluated the efficacy of OG in a CAFs-involved PDAC mouse model. Endothelial-to-mesenchymal transition (EndoMT) is an important source of CAFs. The mix of EndoMT-derived CAFs with PDAC cell grafts significantly recruited myeloid-derived macrophages but prevented immune T cells. HSP90α secreted by EndoMT-derived CAFs further induced macrophage M2-polarization and more HSP90α secretion to expedite PDAC tumor growth. OG exhibited its potent efficacy against the tumor growth, M2-macrophages, and serum HSP90α level in the EndoMT-involved PDAC mouse model. CD91 and TLR4 are cell-surface receptors for extracellular HSP90α (eHSP90α). OG blocked eHSP90α–TLR4 ligation and, thus, prevented eHSP90α-induced M2-macrophages and more HSP90α secretion from macrophages and PDAC cells.
Plasma Proteins and Platelets Modulate Neutrophil Clearance of Malaria-Related Hemozoin Crystals
Authors: Lautenschlager Sueli de Oliveira Silva , Kim Tehyung , Bidóia Danielle Lazarim , Nakamura Celso Vataru , Anders Hans-Joachim , Steiger Stefanie
Published: January 2020

Hemozoin is an insoluble crystalline pigment produced by the malaria parasite Plasmodia upon digesting host hemoglobin inside red blood cells. Red blood cell rupture releases hemozoin crystals into the circulation from where they are cleared by phagocytes such as neutrophils. We speculated that plasma proteins would affect the ability of neutrophils to clear hemozoin crystals. To test this, we cultured human blood neutrophils with hemozoin ex vivo and found that neutrophils ingested hemozoin (0.1–1 µm crystal size) in a dose-dependent manner into phagosomes and vesicles/vacuoles, resulting in morphological changes including nuclear enlargement, and vesicle formation, but not cell membrane rupture or release of neutrophil extracellular traps. The presence of human plasma significantly inhibited the ability of neutrophils to ingest hemozoin crystals. Platelet-poor plasma further inhibited the uptake of hemozoin by neutrophils. Selective exposure to fibrinogen completely replicated the plasma effect. Taken together, neutrophils cleared hemozoin crystals from the extracellular space via endocytosis into phagosomes and vesicles without inducing the release of neutrophil extracellular traps. However, human plasma components such as fibrinogen limited hemozoin clearance, whereas the presence of platelets augmented this process. These factors may influence the pro-inflammatory potential of hemozoin crystals in malaria.
Angiogenic Activity of Cytochalasin B-Induced Membrane Vesicles of Human Mesenchymal Stem Cells
Authors: Gomzikova Marina O. , Zhuravleva Margarita N. , Vorobev Vyacheslav V. , Salafutdinov Ilnur I. , Laikov Alexander V. , Kletukhina Sevindzh K. , Martynova Ekaterina V. , Tazetdinova Leysan G. , Ntekim Atara I. , Khaiboullina Svetlana F. , Rizvanov Albert A.
Published: January 2020

The cytochalasin B-induced membrane vesicles (CIMVs) are suggested to be used as a vehicle for the delivery of therapeutics. However, the angiogenic activity and therapeutic potential of human mesenchymal stem/stromal cells (MSCs) derived CIMVs (CIMVs-MSCs) remains unknown. Objectives: The objectives of this study were to analyze the morphology, size distribution, molecular composition, and angiogenic properties of CIMVs-MSCs. Methods: The morphology of CIMVs-MSC was analyzed by scanning electron microscopy. The proteomic analysis, multiplex analysis, and immunostaining were used to characterize the molecular composition of the CIMVs-MSCs. The transfer of surface proteins from a donor to a recipient cell mediated by CIMVs-MSCs was demonstrated using immunostaining and confocal microscopy. The angiogenic potential of CIMVs-MSCs was evaluated using an in vivo approach of subcutaneous implantation of CIMVs-MSCs in mixture with Matrigel matrix. Results: Human CIMVs-MSCs retain parental MSCs content, such as growth factors, cytokines, and chemokines: EGF, FGF-2, Eotaxin, TGF-α, G-CSF, Flt-3L, GM-CSF, Fractalkine, IFNα2, IFN-γ, GRO, IL-10, MCP-3, IL-12p40, MDC, IL-12p70, IL-15, sCD40L, IL-17A, IL-1RA, IL-1a, IL-9, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IP-10, MCP-1, MIP_1a, MIP-1b, TNF-α, TNF-β, VEGF. CIMVs-MSCs also have the expression of surface receptors similar to those in parental human MSCs (CD90+, CD29+, CD44+, CD73+). Additionally, CIMVs-MSCs could transfer membrane receptors to the surfaces of target cells in vitro. Finally, CIMVs-MSCs can induce angiogenesis in vivo after subcutaneous injection into adult rats. Conclusions: Human CIMVs-MSCs have similar content, immunophenotype, and angiogenic activity to those of the parental MSCs. Therefore, we believe that human CIMVs-MSCs could be used for cell free therapy of degenerative diseases.
Extracellular Vesicles from Mesenchymal Stem Cells as Novel Treatments for Musculoskeletal Diseases
Authors: Alcaraz María José , Compañ Alvaro , Guillén María Isabel
Published: January 2020

Mesenchymal stem/stromal cells (MSCs) represent a promising therapy for musculoskeletal diseases. There is compelling evidence indicating that MSC effects are mainly mediated by paracrine mechanisms and in particular by the secretion of extracellular vesicles (EVs). Many studies have thus suggested that EVs may be an alternative to cell therapy with MSCs in tissue repair. In this review, we summarize the current understanding of MSC EVs actions in preclinical studies of (1) immune regulation and rheumatoid arthritis, (2) bone repair and bone diseases, (3) cartilage repair and osteoarthritis, (4) intervertebral disk degeneration and (5) skeletal muscle and tendon repair. We also discuss the mechanisms underlying these actions and the perspectives of MSC EVs-based strategies for future treatments of musculoskeletal disorders.
Signaling Network of Forkhead Family of Transcription Factors (FOXO) in Dietary Restriction
Authors: Jiang Yizhou , Yan Fengxia , Feng Zhongping , Lazarovici Philip , Zheng Wenhua
Published: January 2020

Dietary restriction (DR), which is defined as a reduction of particular or total nutrient intake without causing malnutrition, has been proved to be a robust way to extend both lifespan and health-span in various species from yeast to mammal. However, the molecular mechanisms by which DR confers benefits on longevity were not yet fully elucidated. The forkhead box O transcription factors (FOXOs), identified as downstream regulators of the insulin/IGF-1 signaling pathway, control the expression of many genes regulating crucial biological processes such as metabolic homeostasis, redox balance, stress response and cell viability and proliferation. The activity of FOXOs is also mediated by AMP-activated protein kinase (AMPK), sirtuins and the mammalian target of rapamycin (mTOR). Therefore, the FOXO-related pathways form a complex network critical for coordinating a response to environmental fluctuations in order to maintain cellular homeostasis and to support physiological aging. In this review, we will focus on the role of FOXOs in different DR interventions. As different DR regimens or calorie (energy) restriction mimetics (CRMs) can elicit both distinct and overlapped DR-related signaling pathways, the benefits of DR may be maximized by combining diverse forms of interventions. In addition, a better understanding of the precise role of FOXOs in different mechanistic aspects of DR response would provide clear cellular and molecular insights on DR-induced increase of lifespan and health-span.
Spontaneous Ultraslow Na+ Fluctuations in the Neonatal Mouse Brain
Authors: Felix Lisa , Ziemens Daniel , Seifert Gerald , Rose Christine
Published: January 2020

In the neonate forebrain, network formation is driven by the spontaneous synchronized activity of pyramidal cells and interneurons, consisting of bursts of electrical activity and intracellular Ca2+ oscillations. By employing ratiometric Na+ imaging in tissue slices obtained from animals at postnatal day 2–4 (P2–4), we found that 22% of pyramidal neurons and 43% of astrocytes in neonatal mouse hippocampus also exhibit transient fluctuations in intracellular Na+. These occurred at very low frequencies (~2/h), were exceptionally long (~8 min), and strongly declined after the first postnatal week. Similar Na+ fluctuations were also observed in the neonate neocortex. In the hippocampus, Na+ elevations in both cell types were diminished when blocking action potential generation with tetrodotoxin. Neuronal Na+ fluctuations were significantly reduced by bicuculline, suggesting the involvement of GABAA-receptors in their generation. Astrocytic signals, by contrast, were neither blocked by inhibition of receptors and/or transporters for different transmitters including GABA and glutamate, nor of various Na+-dependent transporters or Na+-permeable channels. In summary, our results demonstrate for the first time that neonatal astrocytes and neurons display spontaneous ultraslow Na+ fluctuations. While neuronal Na+ signals apparently largely rely on suprathreshold GABAergic excitation, astrocytic Na+ signals, albeit being dependent on neuronal action potentials, appear to have a separate trigger and mechanism, the source of which remains unclear at present.
Novel Mechanistic Insight into the Anticancer Activity of Cucurbitacin D against Pancreatic Cancer (Cuc D Attenuates Pancreatic Cancer)
Authors: Sikander Mohammed , Malik Shabnam , Khan Sheema , Kumari Sonam , Chauhan Neeraj , Khan Parvez , Halaweish Fathi T. , Chauhan Bhavin , Yallapu Murali M. , Jaggi Meena , Chauhan Subhash C.
Published: January 2020

Pancreatic cancer (PanCa) is one of the leading causes of death from cancer in the United States. The current standard treatment for pancreatic cancer is gemcitabine, but its success is poor due to the emergence of drug resistance. Natural products have been widely investigated as potential candidates in cancer therapies, and cucurbitacin D (Cuc D) has shown excellent anticancer properties in various models. However, there is no report on the therapeutic effect of Cuc D in PanCa. In the present study, we investigated the effects of the Cuc D on PanCa cells in vitro and in vivo. Cuc D inhibited the viability of PanCa cells in a dose and time dependent manner, as evident by MTS assays. Furthermore, Cuc D treatment suppressed the colony formation, arrest cell cycle, and decreased the invasion and migration of PanCa cells. Notably, our findings suggest that mucin 13 (MUC13) is down-regulated upon Cuc D treatment, as demonstrated by Western blot and qPCR analyses. Furthermore, we report that the treatment with Cuc D restores miR-145 expression in PanCa cells/tissues. Cuc D treatment suppresses the proliferation of gemcitabine resistant PanCa cells and inhibits RRM1/2 expression. Treatment with Cuc D effectively inhibited the growth of xenograft tumors. Taken together, Cuc D could be utilized as a novel therapeutic agents for the treatment/sensitization of PanCa.
MGL1 Receptor Plays a Key Role in the Control of T. cruzi Infection by Increasing Macrophage Activation through Modulation of ERK1/2, c-Jun, NF-κB and NLRP3 Pathways
Authors: Rodriguez Tonathiu , Pacheco-Fernández Thalia , Vázquez-Mendoza Alicia , Nieto-Yañez Oscar , Juárez-Avelar Imelda , Reyes José L. , Terrazas Luis I. , Rodriguez-Sosa Miriam
Published: January 2020

Macrophage galactose-C type lectin (MGL)1 receptor is involved in the recognition of Trypanosoma cruzi (T. cruzi) parasites and is important for the modulation of the innate and adaptive immune responses. However, the mechanism by which MGL1 promotes resistance to T. cruzi remains unclear. Here, we show that MGL1 knockout macrophages (MGL1−/− Mφ) infected in vitro with T. cruzi were heavily parasitized and showed decreased levels of reactive oxygen species (ROS), nitric oxide (NO), IL-12 and TNF-α compared to wild-type macrophages (WT Mφ). MGL1−/− Mφ stimulated in vitro with T. cruzi antigen (TcAg) showed low expression of TLR-2, TLR-4 and MHC-II, which resulted in deficient splenic cell activation compared with similar co-cultured WT Mφ. Importantly, the activation of p-ERK1/2, p-c-Jun and p-NF-κB p65 were significantly reduced in MGL1−/− Mφ exposed to TcAg. Similarly, procaspase 1, caspase 1 and NLRP3 inflammasome also displayed a reduced expression that was associated with low IL-β production. Our data reveal a previously unappreciated role for MGL1 in Mφ activation through the modulation of ERK1/2, c-Jun, NF-κB and NLRP3 signaling pathways, and to the development of protective innate immunity against experimental T. cruzi infection.
Context-Dependent Strategies for Enhanced Genome Editing of Genodermatoses
Authors: March Oliver Patrick , Kocher Thomas , Koller Ulrich
Published: January 2020

The skin provides direct protection to the human body from assault by the harsh external environment. The crucial function of this organ is significantly disrupted in genodermatoses patients. Genodermatoses comprise a heterogeneous group of largely monogenetic skin disorders, typically involving mutations in genes encoding structural proteins. Therapeutic options for this debilitating group of diseases, including epidermolysis bullosa, primarily consist of wound management. Genome editing approaches co-opt double-strand break repair pathways to introduce desired sequence alterations at specific loci. Rapid advances in genome editing technologies have the potential to propel novel genetic therapies into the clinic. However, the associated phenotypes of many mutations may be treated via several genome editing strategies. Therefore, for potential clinical applications, implementation of efficient approaches based upon mutation, gene and disease context is necessary. Here, we describe current genome editing approaches for the treatment of genodermatoses, along with a discussion of the optimal strategy for each genetic context, in order to achieve enhanced genome editing approaches.
Mfn2 Ablation in the Adult Mouse Hippocampus and Cortex Causes Neuronal Death
Authors: Han Song , Nandy Priya , Austria Quillan , Siedlak Sandra L. , Torres Sandy , Fujioka Hisashi , Wang Wenzhang , Zhu Xiongwei
Published: January 2020

It is believed that mitochondrial fragmentation cause mitochondrial dysfunction and neuronal deficits in Alzheimer’s disease. We recently reported that constitutive knockout of the mitochondria fusion protein mitofusin2 (Mfn2) in the mouse brain causes mitochondrial fragmentation and neurodegeneration in the hippocampus and cortex. Here, we utilize an inducible mouse model to knock out Mfn2 (Mfn2 iKO) in adult mouse hippocampal and cortical neurons to avoid complications due to developmental changes. Electron microscopy shows the mitochondria become swollen with disorganized and degenerated cristae, accompanied by increased oxidative damage 8 weeks after induction, yet the neurons appear normal at the light level. At later timepoints, increased astrocyte and microglia activation appear and nuclei become shrunken and pyknotic. Apoptosis (Terminal deoxynucleotidyl transferase dUTP nick end labeling, TUNEL) begins to occur at 9 weeks, and by 12 weeks, most hippocampal neurons are degenerated, confirmed by loss of NeuN. Prior to the loss of NeuN, aberrant cell-cycle events as marked by proliferating cell nuclear antigen (PCNA) and pHistone3 were evident in some Mfn2 iKO neurons but do not colocalize with TUNEL signals. Thus, this study demonstrated that Mfn2 ablation and mitochondrial fragmentation in adult neurons cause neurodegeneration through oxidative stress and neuroinflammation in vivo via both apoptosis and aberrant cell-cycle-event-dependent cell death pathways.
GDF3 Protects Mice against Sepsis-Induced Cardiac Dysfunction and Mortality by Suppression of Macrophage Pro-Inflammatory Phenotype
Authors: Wang Lu , Li Yutian , Wang Xiaohong , Wang Peng , Essandoh Kobina , Cui Shunan , Huang Wei , Mu Xingjiang , Liu Zhenling , Wang Yigang , Peng Tianqing , Fan Guo-Chang
Published: January 2020

Macrophages are critical for regulation of inflammatory response during endotoxemia and septic shock. However, the mediators underlying their regulatory function remain obscure. Growth differentiation factor 3 (GDF3), a member of transforming growth factor beta (TGF-β) superfamily, has been implicated in inflammatory response. Nonetheless, the role of GDF3 in macrophage-regulated endotoxemia/sepsis is unknown. Here, we show that serum GDF3 levels in septic patients are elevated and strongly correlate with severity of sepsis and 28-day mortality. Interestingly, macrophages treated with recombinant GDF3 protein (rGDF3) exhibit greatly reduced production of pro-inflammatory cytokines, comparing to controls upon endotoxin challenge. Moreover, acute administration of rGDF3 to endotoxin-treated mice suppresses macrophage infiltration to the heart, attenuates systemic and cardiac inflammation with less pro-inflammatory macrophages (M1) and more anti-inflammatory macrophages (M2), as well as prolongs mouse survival. Mechanistically, GDF3 is able to activate Smad2/Smad3 phosphorylation, and consequently inhibits the expression of nod-like receptor protein-3 (NLRP3) in macrophages. Accordingly, blockade of Smad2/Smad3 phosphorylation with SB431542 significantly offsets rGDF3-mediated anti-inflammatory effects. Taken together, this study uncovers that GDF3, as a novel sepsis-associated factor, may have a dual role in the pathophysiology of sepsis. Acute administration of rGDF3 into endotoxic shock mice could increase survival outcome and improve cardiac function through anti-inflammatory response by suppression of M1 macrophage phenotype. However, constitutive high levels of GDF3 in human sepsis patients are associated with lethality, suggesting that GDF3 may promote macrophage polarization toward M2 phenotype which could lead to immunosuppression.
Complementary Parent Components for Pediatric Pain Families: Innovations in Treatment
Authors: Russell Beth S. , Guite Jessica W. , Homan Kendra J. , Tepe Rebecca M. , Williams Sara E.
Published: January 2020

For families with a child with chronic pain, the home environment is the context in which adaptive or maladaptive illness behaviors are developed. Supporting families to effectively cope with their child’s chronic pain is a critical need. This work analyzes intervention approaches from emerging treatment programs to support families coping with pediatric pain that diverge from traditional treatment models by specifically targeting parents. Two novel parent intervention programs are presented that consider caregiver needs in both outpatient and inpatient pain treatment settings: Parents as Coping Coaches and Putting Parents FIRST. These programs are evaluated through comparing parental training components across different stages of treatment. Additionally, the efficacy of Putting Parents FIRST in promoting maintenance of children’s functional gains achieved in intensive interdisciplinary pain treatment is presented, and compared to previous results of the efficacy of Putting Parents FIRST. Specifically, outcomes of 36 children whose parents received the intervention in Putting Parents FIRST were compared to a matched control sample of children whose parents did not receive the parent intervention. Similar to the findings from Parents as Coping Coaches, results indicated that patients whose parents received the intervention maintained/improved program gains in disability, coping, and pain significantly more than patients whose parents did not receive the intervention. Implications for parent-focused intervention development efforts targeting parent and youth functioning in the context of pediatric chronic pain are considered.
Design of Bioinspired Emulsified Composite European Eel Gelatin and Protein Isolate-Based Food Packaging Film: Thermal, Microstructural, Mechanical, and Biological Features
Authors: Taktak Wafa , Kchaou Hela , Hamdi Marwa , Li Suming , Nasri Moncef , Karra-Chaâbouni Maha , Nasri Rim
Published: January 2020

The study focused on the elaboration and the characterization of blend biofilms based on European eel skin gelatin (ESG) and protein isolate (EPI) and the assessment of European oil (EO) incorporation effect on their properties. Data displayed that the incorporation of EPI and EO to the gelatin formulation decreased the lightness and yellowness of composite and emulsified films, respectively, compared to ESG film. Moreover, ESG films exhibited improved mechanical properties than EPI films. FTIR analysis, all incorporated films with EO at the ratio 1:4 (oil/polymer) revealed similar characteristic bands as in free-oil films. Further, the SEM images of 100% ESG and 100% EPI films showed a smooth and homogenous structure, whereas the cross-section of blend film (at a ratio 50:50) displayed a rougher microstructure. In addition, emulsified film ESG100 revealed a smooth and homogeneous microstructure compared to that prepared using EPI/ESG 50/50 ratio. Furthermore, EPI or EO addition into the ESG matrix enhanced the blend films antioxidant activities.