To detect and monitor G-group aflatoxins in agricultural products, we generated class-specific monoclonal antibodies that specifically recognized aflatoxins G1 and G2. Of the final three positive and stable hybridomas obtained, clone 2G6 produced a monoclonal antibody that had equal sensitivity to aflatoxins G1 and G2, and did not cross-react with aflatoxins B1, B2, or M1. Its IC50 values for aflatoxins G1 and G2 were 17.18 ng·mL−1 and 19.75 ng·mL−1, respectively. Using this new monoclonal antibody, we developed a competitive indirect enzyme-linked immunosorbent assay (CI-ELISA); the method had a limit of detection of 0.06 ng·mL−1. To validate this CI-ELISA, we spiked uncontaminated peanut samples with various amounts of aflatoxins G1 and G2 and compared recovery rates with those determined by a standard HPLC method. The recovery rates of the CI-ELISA ranging from 94% to 103% were comparable to those of the HPLC (92% to 102%). We also used both methods to determine the amounts of G-group aflatoxins in five peanut samples contaminated by aflatoxin B1-positive, and their relative standard deviations ranged from 8.4% to 17.7% (under 20%), which demonstrates a good correlation between the two methods. We further used this CI-ELISA to assess the ability of 126 fungal strains isolated from peanuts or field soils to produce G-group aflatoxins. Among these, seven stains producing different amounts of G-group aflatoxins were identified. Our results showed that the monoclonal antibody 2 G6-based CI-ELISA was suitable for the detection of G-group aflatoxins present in peanuts and also those produced by fungi.
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Δευτέρα 28 Δεκεμβρίου 2015
Toxins, Vol. 8, Pages 5: Development of an Enzyme-Linked Immunosorbent Assay Method Specific for the Detection of G-Group Aflatoxins
Influence of the Alcohol Present in a Phytotherapic Tincture on Male Rat Lipid Profiles and Renal Function
This study evaluated the influence of the alcohol present in a formulation of the antiophidic phytotherapic tincture, Específico-Pessôa, on rat blood biochemical and hematological parameters, and on organ histology. Three groups of rats were treated orally for 10, 15, or 30 days; one group received the tincture, the other received alcohol alone, and the third was a control group. The results of this study indicated that cholesterol levels were significantly increased after 10 days in the alcohol and tincture groups, although these decreased after 30 days in the tincture group. Triglyceride levels were significantly reduced after 15 days in the tincture group and after 30 days in the alcohol and tincture groups. A higher creatinine level was observed in the alcohol and tincture groups after 15 and 30 days. The uric acid levels in these groups were reduced at 10 and 30 days, although this metabolite was elevated at 15 days in the alcohol group. Hydropic multifocal degeneration with lymphohistiocytic infiltration and some polymorphonuclear cells was observed in the livers of rats treated with either the tincture or alcohol. These data demonstrate the importance of considering the potential actions of the alcohol present in pharmaceutical formulations.
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Energies, Vol. 9, Pages 18: Performance Characteristics of a Modularized and Integrated PTC Heating System for an Electric Vehicle
A modularized positive temperature coefficient heating system has controller-integrated heater modules. Such a heating system that uses a high-voltage power of 330 V was developed in the present study for use in electric vehicles. Four heater modules and one controller with an input power of 5.6 kW were integrated in the modularized system, which was designed for improved heating power density and light weight compared to the conventional heating system, in which the controller is separated. We experimentally investigated the performance characteristics, namely, the heating capacity, energy efficiency, and pressure drop, of a prototype of the developed heating system and found it to have satisfactory performance. The findings of this study will contribute to the development of heating systems for electric vehicles.
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Molecules, Vol. 21, Pages 8: The Synthesis of the Metabolites of 2′,3′,5′-Tri-O-acetyl-N6-(3-hydroxyphenyl) Adenosine (WS070117)
Seven metabolites of 2′,3′,5′-tri-O-acetyl-N6-(3-hydroxyphenyl) adenosine (WS070117) were synthesized by deacetylation, hydrolysis, cyclization, sulfonylation and glycosylation reactions, respectively. All these compounds, which could be useful as material standards for metabolic research, were characterized by NMR and HPLC-MS (ESI) analyses.
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Symmetry, Vol. 8, Pages 1: Structural Properties and Biological Prediction of ({[(1E)-3-(1H-Imidazol-1-yl)-1-phenylpropylidene] amino}oxy)(4-methylphenyl)methanone: An In Silico Approach
Bioactive molecules are playing essential role in the field of drug discovery and various pharmaceutical applications. Vibrational spectral investigations of the anti-Candida agent ({[(1E)-3-(1H-imidazol-1-yl)-1-phenylpropylidene]amino}oxy)(4-methylphenyl)methanone ((1E)-IPMM) have been recorded and analyzed to understand its structural geometry, inter- and intra-molecular interactions. The equilibrium geometry, harmonic vibrational wavenumber, natural bond orbital (NBO) and Frontier orbital energy analyses have been carried out with the help of density functional theory with B3LYP/6-311++G(d,p) level of theory. The detailed vibrational assignments for the title molecule were performed on the basis of potential energy distribution analysis in order to unambiguously predict its modes. The calculated wavenumbers had good agreement with the experimental values. NBO analysis has confirmed the intramolecular charge transfer interactions. The predicted docking binding energy gave insight into the possible biological activity of the title molecule.
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Molecules, Vol. 21, Pages 31: Terpenoids from the Marine-Derived Fungus Aspergillus fumigatus YK-7
Two new β-bergamotane sesquiterpenoids, E-β-trans-5,8,11-trihydroxybergamot-9-ene (1) and β-trans-2β,5,15-trihydroxybergamot-10-ene (2), were isolated from the marine-derived fungus Aspergillus fumigatus YK-7, along with three known terpenoids 3–5. Their structures were determined by spectroscopic methods (1D and 2D NMR, HR-ESI-MS). Antiproliferative effects on human leukemic monocyte lymphoma U937 and human prostate cancer PC-3 cell lines were measured in vitro. Compound 4 exhibited potent activity against the U937 cell line with an IC50 value of 4.2 μM.
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Sensors, Vol. 16, Pages 34: The Performance Analysis of the Map-Aided Fuzzy Decision Tree Based on the Pedestrian Dead Reckoning Algorithm in an Indoor Environment
Hardware sensors embedded in a smartphone allow the device to become an excellent mobile navigator. A smartphone is ideal for this task because its great international popularity has led to increased phone power and since most of the necessary infrastructure is already in place. However, using a smartphone for indoor pedestrian navigation can be problematic due to the low accuracy of sensors, imprecise predictability of pedestrian motion, and inaccessibility of the Global Navigation Satellite System (GNSS) in some indoor environments. Pedestrian Dead Reckoning (PDR) is one of the most common technologies used for pedestrian navigation, but in its present form, various errors tend to accumulate. This study introduces a fuzzy decision tree (FDT) aided by map information to improve the accuracy and stability of PDR with less dependency on infrastructure. First, the map is quickly surveyed by the Indoor Mobile Mapping System (IMMS). Next, Bluetooth beacons are implemented to enable the initializing of any position. Finally, map-aided FDT can estimate navigation solutions in real time. The experiments were conducted in different fields using a variety of smartphones and users in order to verify stability. The contrast PDR system demonstrates low stability for each case without pre-calibration and post-processing, but the proposed low-complexity FDT algorithm shows good stability and accuracy under the same conditions.
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Buildings, Vol. 6, Pages 1: Acoustic Intervention in a Cultural Heritage: The Chapel of the Royal Palace in Caserta, Italy
The modern use of ancient heritage sites can be, to say the least, challenging from an acoustical perspective. In fact, modern needs may require acoustical interventions in contrast with the preservation issues of the cultural heritage. This paper deals with this topic in an UNESCO designated world heritage site, the Palatine Chapel of the Royal Palace in Caserta, Italy. Since this chapel is currently being used for meetings and music chamber concerts, the acoustical characteristics of the chapel, originally used for religious purposes, are investigated. Field measurements were undertaken to evaluate the acoustical performance of the empty chapel. The measurements were then used to calibrate and validate a computer simulation model. Different acoustical treatments are then considered and simulations are used to determine the related acoustical improvements. Finally, the benefits of different acoustical treatments which are respectful of the aesthetic and historical value of this cultural heritage are discussed.
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Nutrients, Vol. 8, Pages 11: Clustering of Dietary Patterns, Lifestyles, and Overweight among Spanish Children and Adolescents in the ANIBES Study
Weight gain has been associated with behaviors related to diet, sedentary lifestyle, and physical activity. We investigated dietary patterns and possible meaningful clustering of physical activity, sedentary behavior, and sleep time in Spanish children and adolescents and whether the identified clusters could be associated with overweight. Analysis was based on a subsample (n = 415) of the cross-sectional ANIBES study in Spain. We performed exploratory factor analysis and subsequent cluster analysis of dietary patterns, physical activity, sedentary behaviors, and sleep time. Logistic regression analysis was used to explore the association between the cluster solutions and overweight. Factor analysis identified four dietary patterns, one reflecting a profile closer to the traditional Mediterranean diet. Dietary patterns, physical activity behaviors, sedentary behaviors and sleep time on weekdays in Spanish children and adolescents clustered into two different groups. A low physical activity-poorer diet lifestyle pattern, which included a higher proportion of girls, and a high physical activity, low sedentary behavior, longer sleep duration, healthier diet lifestyle pattern. Although increased risk of being overweight was not significant, the Prevalence Ratios (PRs) for the low physical activity-poorer diet lifestyle pattern were >1 in children and in adolescents. The healthier lifestyle pattern included lower proportions of children and adolescents from low socioeconomic status backgrounds.
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Religions, Vol. 7, Pages 4: “This Is Our Jerusalem”: Early American Evangelical Localizations of the Hebraic Republic
This paper examines how evangelical pastors applied Protestant notions of a Hebraic Republic for their parishioners as America transitioned from a colonial frontier to a new republic. As the American constitutions took shape during and after the Revolution, many evangelical pastors argued that America emulated or was inspired by the Israelite polity as described by the Old Testament. America and its institutions thus became a reincarnated Hebraic Republic, a new "city on a hill", and a new Jerusalem. Originally these pastors drew on a broader, global movement that was shaping republican attempts at reform in Europe, but as they localized the biblical model to their own particular experiences, they brought new meaning to it and exported the transformed model back out to the world.
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Sensors, Vol. 16, Pages 35: Effects of Operating Parameters on Measurements of Biochemical Oxygen Demand Using a Mediatorless Microbial Fuel Cell Biosensor
The conventional Biochemical Oxygen Demand (BOD) method takes five days to analyze samples. A microbial fuel cell (MFC) may be an alternate tool for rapid BOD determination in water. However, a MFC biosensor for continuous BOD measurements of water samples is still unavailable. In this study, a MFC biosensor inoculated with known mixed cultures was used to determine the BOD concentration. Effects of important parameters on establishing a calibration curve between the BOD concentration and output signal from the MFC were evaluated. The results indicate monosaccharides were good fuel, and methionine, phenylalanine, and ethanol were poor fuels for electricity generation by the MFC. Ions in the influent did not significantly affect the MFC performance. CN− in the influent could alleviate the effect of antagonistic electron acceptors on the MFC performance. The regression equation for BOD concentration and current density of the biosensor was y = 0.0145x + 0.3317. It was adopted to measure accurately and continuously the BOD concentration in actual water samples at an acceptable error margin. These results clearly show the developed MFC biosensor has great potential as an alternative BOD sensing device for online measurements of wastewater BOD.
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Sustainability, Vol. 8, Pages 26: The Optimization of Cyclic Links of Live Pig-Industry Chain Based on Circular Economics
To reduce waste and wastewater pollution and to improve the utilization rate of resources in the pig-industry chain, a circular economy of the chain can be developed. The key to constructing the circular economic system of the pig-industry chain is to determine the path of the cyclic materials and to design reasonable waste- and wastewater-treatment capacities. This paper focuses on the treatment and recycling of wastewater in the pig-industry chain and the treatment and recycling of waste into manure and feed. After giving the two circular paths, the paper proposes a multi-objective uncertainty-optimization model for the cyclic links of the pig-industry chain with the highest resource-reuse efficiency and the lowest construction cost based on the uncertainty of market demand. Using a combination of the neural network and genetic algorithm method for designing the solution process for the model, the paper finally introduces the determination methods of relevant parameters and verifies the feasibility and effectiveness of the model through a case study.
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Nanomaterials, Vol. 6, Pages 3: Receptor-Mediated Drug Delivery Systems Targeting to Glioma
Glioma has been considered to be the most frequent primary tumor within the central nervous system (CNS). The complexity of glioma, especially the existence of the blood-brain barrier (BBB), makes the survival and prognosis of glioma remain poor even after a standard treatment based on surgery, radiotherapy, and chemotherapy. This provides a rationale for the development of some novel therapeutic strategies. Among them, receptor-mediated drug delivery is a specific pattern taking advantage of differential expression of receptors between tumors and normal tissues. The strategy can actively transport drugs, such as small molecular drugs, gene medicines, and therapeutic proteins to glioma while minimizing adverse reactions. This review will summarize recent progress on receptor-mediated drug delivery systems targeting to glioma, and conclude the challenges and prospects of receptor-mediated glioma-targeted therapy for future applications.
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Humanities, Vol. 5, Pages 3: On Sound: Reconstructing a Zhuangzian Perspective of Music
A devotion to music in Chinese classical texts is worth noticing. Early Chinese thinkers saw music as a significant part of human experience and a core practice for philosophy. While Confucian endorsement of ritual and music has been discussed in the field, Daoist understanding of music was hardly explored. This paper will make a careful reading of the Xiánchí 咸池 music story in the Zhuangzi, one of the most interesting, but least noticed texts, and reconstruct a Zhuangzian perspective from it. While sounds had been regarded as mere building blocks of music and thus depreciated in the hierarchical understanding of music in the mainstream discourse of early China, sound is the alpha and omega of music in the Zhuangzian perspective. All kinds of sounds, both human and natural, are invited into musical discourse. Sound is regarded as the real source of our being moved by music, and therefore, musical consummation is depicted as embodiment through sound.
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Toxins, Vol. 8, Pages 5: Development of an Enzyme-Linked Immunosorbent Assay Method Specific for the Detection of G-Group Aflatoxins
To detect and monitor G-group aflatoxins in agricultural products, we generated class-specific monoclonal antibodies that specifically recognized aflatoxins G1 and G2. Of the final three positive and stable hybridomas obtained, clone 2G6 produced a monoclonal antibody that had equal sensitivity to aflatoxins G1 and G2, and did not cross-react with aflatoxins B1, B2, or M1. Its IC50 values for aflatoxins G1 and G2 were 17.18 ng·mL−1 and 19.75 ng·mL−1, respectively. Using this new monoclonal antibody, we developed a competitive indirect enzyme-linked immunosorbent assay (CI-ELISA); the method had a limit of detection of 0.06 ng·mL−1. To validate this CI-ELISA, we spiked uncontaminated peanut samples with various amounts of aflatoxins G1 and G2 and compared recovery rates with those determined by a standard HPLC method. The recovery rates of the CI-ELISA ranging from 94% to 103% were comparable to those of the HPLC (92% to 102%). We also used both methods to determine the amounts of G-group aflatoxins in five peanut samples contaminated by aflatoxin B1-positive, and their relative standard deviations ranged from 8.4% to 17.7% (under 20%), which demonstrates a good correlation between the two methods. We further used this CI-ELISA to assess the ability of 126 fungal strains isolated from peanuts or field soils to produce G-group aflatoxins. Among these, seven stains producing different amounts of G-group aflatoxins were identified. Our results showed that the monoclonal antibody 2 G6-based CI-ELISA was suitable for the detection of G-group aflatoxins present in peanuts and also those produced by fungi.
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Atmosphere, Vol. 7, Pages 3: Erratum: Hassan, M.; et al. An Assessment of the South Asian Summer Monsoon Variability for Present and Future Climatologies Using a High Resolution Regional Climate Model (RegCM4.3) under the AR5 Scenarios. Atmosphere 2015, 6, 1833–1857
The published date in the paper [1] should be 23 November 2015. We apologize to the authors of the paper and readers of Atmosphere for any inconvenience caused. [...]
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Systems, Vol. 4, Pages 2: A Research on Active Control to Synchronize a New 3D Chaotic System
This paper presents the robust synchronization problem of a 3D chaotic system by using the active control technique. Based on the Gershgorin theorem and Routh-Hurwitz criterion, sufficient algebraic conditions are derived to design a linear controller gain matrix. The conditions are then applied for the robust stability of the synchronization error dynamics in the presence of an unknown bounded smooth external disturbance. The proposed active control strategy with a suitable computation of the linear controller gain matrix is simple in design and establishes fast convergence rates of the synchronization error signals. Numerical simulation results further verified the analytical results.
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Nutrients, Vol. 8, Pages 16: Role of Chlorogenic Acids in Controlling Oxidative and Inflammatory Stress Conditions
Chlorogenic acids (CGAs) are esters formed between caffeic and quinic acids, and represent an abundant group of plant polyphenols present in the human diet. CGAs have different subgroups that include caffeoylquinic, p-coumaroylquinic, and feruloyquinic acids. Results of epidemiological studies suggest that the consumption of beverages such as coffee, tea, wine, different herbal infusions, and also some fruit juices is linked to reduced risks of developing different chronic diseases. These beverages contain CGAs present in different concentrations and isomeric mixtures. The underlying mechanism(s) for specific health benefits attributed to CGAs involves mitigating oxidative stress, and hence the related adverse effects associated with an unbalanced intracellular redox state. There is also evidence to show that CGAs exhibit anti-inflammatory activities by modulating a number of important metabolic pathways. This review will focus on three specific aspects of the relevance of CGAs in coffee beverages; namely: (1) the relative composition of different CGA isomers present in coffee beverages; (2) analysis of in vitro and in vivo evidence that CGAs and individual isomers can mitigate oxidative and inflammatory stresses; and (3) description of the molecular mechanisms that have a key role in the cell signaling activity that underlines important functions.
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IJMS, Vol. 17, Pages 37: The Role of bFGF in the Excessive Activation of Astrocytes Is Related to the Inhibition of TLR4/NFκB Signals
Astrocytes have critical roles in immune defense, homeostasis, metabolism, and synaptic remodeling and function in the central nervous system (CNS); however, excessive activation of astrocytes with increased intermediate filaments following neuronal trauma, infection, ischemia, stroke, and neurodegenerative diseases results in a pro-inflammatory environment and promotes neuronal death. As an important neurotrophic factor, the secretion of endogenous basic fibroblast growth factor (bFGF) contributes to the protective effect of neuronal cells, but the mechanism of bFGF in reactive astrogliosis is still unclear. In this study, we demonstrated that exogenous bFGF attenuated astrocyte activation by reducing the expression of glial fibrillary acidic protein (GFAP) and other markers, including neurocan and vimentin, but not nestin and decreased the levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), via the regulation of the upstream toll-like receptor 4/nuclear factor κB (TLR4/NFκB) signaling pathway. Our study suggests that the function of bFGF is not only related to the neuroprotective and neurotrophic effect but also involved in the inhibition of excessive astrogliosis and glial scarring after neuronal injury.
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IJMS, Vol. 17, Pages 33: Targeted Radionuclide Therapy of Human Tumors
Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed.
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IJMS, Vol. 17, Pages 25: Interleukin-10 Protection against Lipopolysaccharide-Induced Neuro-Inflammation and Neurotoxicity in Ventral Mesencephalic Cultures
Interleukin (IL)-10, an anti-inflammatory cytokine, is expressed in the brain and can inhibit microglial activation. Herein, we utilized lipopolysaccharide (LPS)-induced inflammatory Parkinson's disease (PD) cell model to determine whether microglia and astrocytes are necessary targets for IL-10 neuroprotection. Primary ventral mesencephalic (VM) cultures with different composition of neurons, microglia and astrocytes were prepared. The cells were exposed to IL-10 (15, 50 or 150 ng/mL) 1 h prior to LPS (50 ng/mL) treatment. LPS induced dopaminergic and non-dopaminergic neuronal loss in VM cultures, VM neuron-enriched cultures, and neuron-microglia co-cultures, but not in neuron-astrocyte co-cultures. IL-10 reduced LPS-induced neuronal loss particularly in single VM neuron cultures. Pro-inflammatory mediators (TNF-α, IL-1β, inducible nitric oxide synthase and cyclooxygenase-2) were upregulated in both neuron-microglia and neuron-astrocyte co-cultures by LPS. In contrast, neurotrophic factors (brain-derived neurotrophic factor, insulin-like growth factor-1 or glial cell-derived neurotrophic factor) were downregulated in neuron-microglia co-cultures, but upregulated in neuron-astrocyte co-cultures by LPS. IL-10 reduced both the increase in production of the pro-inflammatory mediators and the decrease in production of the neurotrophic factors induced by LPS. These results suggest that astrocytes can balance LPS neurotoxicity by releasing more neurotrophic factors and that IL-10 exerts neuroprotective property by an extensive action including direct on neurons and indirect via inhibiting microglial activation.
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Sustainability, Vol. 8, Pages 25: Using Social Media for Emergency Response and Urban Sustainability: A Case Study of the 2012 Beijing Rainstorm
With the proliferation of social media, information generated and disseminated from these outlets has become an important part of our everyday lives. For example, this type of information has great potential for effectively distributing political messages, hazard alerts, or messages of other social functions. In this work, we report a case study of the 2012 Beijing Rainstorm to investigate how emergency information was timely distributed using social media during emergency events. We present a classification and location model for social media text streams during emergency events. This model classifies social media text streams based on their topical contents. Integrated with a trend analysis, we show how Sina-Weibo fluctuated during emergency events. Using a spatial statistical analysis method, we found that the distribution patterns of Sina-Weibo were related to the emergency events but varied among different topics. This study helps us to better understand emergency events so that decision-makers can act on emergencies in a timely manner. In addition, this paper presents the tools, methods, and models developed in this study that can be used to work with text streams from social media in the context of disaster management and urban sustainability.
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IJMS, Vol. 17, Pages 33: Targeted Radionuclide Therapy of Human Tumors
Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed.
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Molecules, Vol. 21, Pages 26: Strong and Nonspecific Synergistic Antibacterial Efficiency of Antibiotics Combined with Silver Nanoparticles at Very Low Concentrations Showing No Cytotoxic Effect
The resistance of bacteria towards traditional antibiotics currently constitutes one of the most important health care issues with serious negative impacts in practice. Overcoming this issue can be achieved by using antibacterial agents with multimode antibacterial action. Silver nano-particles (AgNPs) are one of the well-known antibacterial substances showing such multimode antibacterial action. Therefore, AgNPs are suitable candidates for use in combinations with traditional antibiotics in order to improve their antibacterial action. In this work, a systematic study quantifying the synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus was performed. Employing the microdilution method as more suitable and reliable than the disc diffusion method, strong synergistic effects were shown for all tested antibiotics combined with AgNPs at very low concentrations of both antibiotics and AgNPs. No trends were observed for synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs, indicating non-specific synergistic effects. Moreover, a very low amount of silver is needed for effective antibacterial action of the antibiotics, which represents an important finding for potential medical applications due to the negligible cytotoxic effect of AgNPs towards human cells at these concentration levels.
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IJMS, Vol. 17, Pages 25: Interleukin-10 Protection against Lipopolysaccharide-Induced Neuro-Inflammation and Neurotoxicity in Ventral Mesencephalic Cultures
Interleukin (IL)-10, an anti-inflammatory cytokine, is expressed in the brain and can inhibit microglial activation. Herein, we utilized lipopolysaccharide (LPS)-induced inflammatory Parkinson's disease (PD) cell model to determine whether microglia and astrocytes are necessary targets for IL-10 neuroprotection. Primary ventral mesencephalic (VM) cultures with different composition of neurons, microglia and astrocytes were prepared. The cells were exposed to IL-10 (15, 50 or 150 ng/mL) 1 h prior to LPS (50 ng/mL) treatment. LPS induced dopaminergic and non-dopaminergic neuronal loss in VM cultures, VM neuron-enriched cultures, and neuron-microglia co-cultures, but not in neuron-astrocyte co-cultures. IL-10 reduced LPS-induced neuronal loss particularly in single VM neuron cultures. Pro-inflammatory mediators (TNF-α, IL-1β, inducible nitric oxide synthase and cyclooxygenase-2) were upregulated in both neuron-microglia and neuron-astrocyte co-cultures by LPS. In contrast, neurotrophic factors (brain-derived neurotrophic factor, insulin-like growth factor-1 or glial cell-derived neurotrophic factor) were downregulated in neuron-microglia co-cultures, but upregulated in neuron-astrocyte co-cultures by LPS. IL-10 reduced both the increase in production of the pro-inflammatory mediators and the decrease in production of the neurotrophic factors induced by LPS. These results suggest that astrocytes can balance LPS neurotoxicity by releasing more neurotrophic factors and that IL-10 exerts neuroprotective property by an extensive action including direct on neurons and indirect via inhibiting microglial activation.
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Molecules, Vol. 21, Pages 44: Site-Selective Ribosylation of Fluorescent Nucleobase Analogs Using Purine-Nucleoside Phosphorylase as a Catalyst: Effects of Point Mutations
Enzymatic ribosylation of fluorescent 8-azapurine derivatives, like 8-azaguanine and 2,6-diamino-8-azapurine, with purine-nucleoside phosphorylase (PNP) as a catalyst, leads to N9, N8, and N7-ribosides. The final proportion of the products may be modulated by point mutations in the enzyme active site. As an example, ribosylation of the latter substrate by wild-type calf PNP gives N7- and N8-ribosides, while the N243D mutant directs the ribosyl substitution at N9- and N7-positions. The same mutant allows synthesis of the fluorescent N7-β-d-ribosyl-8-azaguanine. The mutated form of the E. coli PNP, D204N, can be utilized to obtain non-typical ribosides of 8-azaadenine and 2,6-diamino-8-azapurine as well. The N7- and N8-ribosides of the 8-azapurines can be analytically useful, as illustrated by N7-β-d-ribosyl-2,6-diamino-8-azapurine, which is a good fluorogenic substrate for mammalian forms of PNP, including human blood PNP, while the N8-riboside is selective to the E. coli enzyme.
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IJMS, Vol. 17, Pages 37: The Role of bFGF in the Excessive Activation of Astrocytes Is Related to the Inhibition of TLR4/NFκB Signals
Astrocytes have critical roles in immune defense, homeostasis, metabolism, and synaptic remodeling and function in the central nervous system (CNS); however, excessive activation of astrocytes with increased intermediate filaments following neuronal trauma, infection, ischemia, stroke, and neurodegenerative diseases results in a pro-inflammatory environment and promotes neuronal death. As an important neurotrophic factor, the secretion of endogenous basic fibroblast growth factor (bFGF) contributes to the protective effect of neuronal cells, but the mechanism of bFGF in reactive astrogliosis is still unclear. In this study, we demonstrated that exogenous bFGF attenuated astrocyte activation by reducing the expression of glial fibrillary acidic protein (GFAP) and other markers, including neurocan and vimentin, but not nestin and decreased the levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), via the regulation of the upstream toll-like receptor 4/nuclear factor κB (TLR4/NFκB) signaling pathway. Our study suggests that the function of bFGF is not only related to the neuroprotective and neurotrophic effect but also involved in the inhibition of excessive astrogliosis and glial scarring after neuronal injury.
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BioEssays 1∕2016
Mitochondria modulate gene expression. On pages 64–76 Guantes et al. discuss how mitochondrial content influences cellular heterogeneity through its impact on gene expression. The cover shows an electron micrograph of one mitochondrion with radiating arrows to the steps of gene expression where mitochondria play a role.
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Pluripotency and the endogenous retrovirus HERVH: Conflict or serendipity?
Remnants of ancient retroviral infections during evolution litter all mammalian genomes. In modern humans, such endogenous retroviral (ERV) sequences comprise at least 8% of the genome. While ERVs and other types of transposable elements undoubtedly contribute to the genomic "junk yard", functions for some ERV sequences have been demonstrated, with growing evidence that ERVs can be important players in gene regulatory processes. Here we focus on one particular large family of human ERVs, termed HERVH, which several recent studies suggest has a key regulatory role in human pluripotent stem cells. Remarkably, this is not the first instance of an ERV controlling pluripotency. We speculate as to why this convergent evolution might have come about, suggesting that it may reflect selection on the virus to extend the time available for transposition. Alternatively it may reflect serendipity alone.
Our genome harbors ∼2000 copies of the retroviral element HERVH, which have accumulated by infections and retrotranspositions over time. This endogenization process resulted in some HERVH copies acquiring a domesticated cellular function. In primates, HERVH drives a regulatory network modulating pluripotency. We ask why similar events occur repeatedly during evolution.
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Potentially Functional Polymorphisms in POU5F1 Gene Are Associated with the Risk of Lung Cancer in Han Chinese
POU5F1 is a key regulator of self-renewal and differentiation in embryonic stem cells and may be associated with initiation, promotion, and progression in cancer. We hypothesized that functional polymorphisms in POU5F1 may play an important role in modifying the lung cancer risk. To test this hypothesis, we conducted a case-control study to explore the association between 17 potentially functional SNPs in POU5F1 gene and the lung cancer risk in 1,341 incident lung cancer cases and 1,982 healthy controls in a Chinese population. We found that variant alleles of rs887468 and rs3130457 were significantly associated with increased risk of lung cancer after multiple comparison (OR = 1.29, 95% CI: 1.11–1.51, for rs887468; OR = 1.29, 95% CI: 1.10–1.51, for rs3130457, resp.). In addition, we detected a significant interaction between rs887468 genotypes and smoking status on lung cancer risk (). Combined analysis of these 2 SNPs showed a significant allele-dosage association between the number of risk alleles and increased risk of lung cancer (). These findings indicate that potentially functional polymorphisms in POU5F1 gene may contribute to lung cancer susceptibility in a Chinese population.
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Exercise oxidative skeletal muscle metabolism in adolescents with cystic fibrosis
Introduction: Patients with Cystic Fibrosis (CF) are reported to have limited exercise capacity. There is no consensus about a possible abnormality in skeletal muscle oxidative metabolism in CF. Our aim is to test the hypothesis that abnormalities in oxygenation and/or muscle oxidative metabolism contribute to exercise intolerance in adolescents with mild CF. Methods: Ten adolescents with CF (12-18 years of age, FEV1>80%pred, resting oxygen saturation > 94%) and ten healthy age-matched controls (HC) were tested with supine cycle ergometry using near-infrared spectroscopy (NIRS) and 31Phosphorus magnetic resonance spectroscopy (31P MRS) to study skeletal muscle oxygenation and oxidative metabolism during rest, exercise and recovery. Results: No statistically significant (p>0.1) differences in peak workload and peak oxygen uptake per kilogram lean body mass were found between CF and HC. No differences were found between CF and HC in bulk changes of quadriceps phosphocreatine (PCr) (p = .550) and inorganic phosphate (Pi) (p = .896) content and pH (p = .512) during symptom limited exercise. Furthermore, we found statistically identical kinetics for PCr resynthesis during recovery for CF and HC (p = .53). No statistically significant difference in peak exercise arbitrary unit for total haemoglobin content (tHb_AU) was found between CF and HC (p = .66). Discussion: The results of this study provide evidence that in patients with mild CF and a stable clinical status (without signs of systemic inflammation and /or chronic PA colonisation), no intrinsic metabolic constraints and/or abnormalities in oxygenation and/or muscle oxidative metabolism contribute to exercise intolerance.
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Arginase inhibition improves endothelial function in patients with familial hypercholesterolaemia irrespective of their cholesterol levels
Abstract
Background
Elevated LDL cholesterol is an important risk factor for atherosclerosis. Endothelial dysfunction, an early event in the development of atherosclerosis, is characterized by a reduction in nitric oxide (NO) bioavailability. Arginase has emerged as a key regulator of endothelial function through competition with NO synthase for the common substrate l-arginine. Arginase in endothelial cells is activated by oxidized LDL. The study aim was to investigate the importance of arginase for endothelial dysfunction in patients with familial hypercholesterolaemia (FH).
Methods and results
Endothelial function was evaluated in 12 patients with heterozygous FH and 12 age-matched healthy normocholesterolaemic subjects using forearm venous occlusion plethysmography. The evaluations in FH patients occurred when they were on lipid-lowering therapy and 4 weeks after withdrawal of treatment. Endothelium-dependent vasodilatation (EDV) was assessed by intrabrachial artery infusion of serotonin, and endothelium-independent dilatation was assessed by infusion of nitroprusside before and after 120 min administration of the arginase inhibitor N ω-hydroxy-nor-l-arginine (nor-NOHA; 0.1 mg min−1). In FH patients LDL cholesterol increased from 4.3 ± 0.9 mmol L−1 at baseline to 7.6 ± 1.9 mmol L−1 at follow-up (P < 0.001). Arginase inhibition enhanced EDV in FH patients by a similar degree independent of lipid-lowering therapy. The improvement in EDV by arginase inhibition was significantly greater in FH patients than in the control group.
Conclusion
Arginase inhibition results in greater improvement in endothelial function in patients with FH compared to healthy controls irrespective of their cholesterol levels. Arginase may be a promising therapeutic target for improving endothelial function in patients with hypercholesterolaemia.
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Prognostic indices in chronic lymphocytic leukaemia: where do we stand how do we proceed?
Abstract
The remarkable clinical heterogeneity in chronic lymphocytic leukaemia (CLL) has highlighted the need for prognostic and predictive algorithms that can be employed in clinical practice to assist patient management and therapy decisions. Over the last 20 years, this research field has been rewarding and many novel prognostic factors have been identified, especially at the molecular genetic level. Whilst detection of recurrent cytogenetic aberrations and determination of the immunoglobulin heavy variable gene somatic hypermutation status have an established role in outcome prediction, next-generation sequencing has recently revealed novel mutated genes with clinical relevance (e.g. NOTCH1, SF3B1 and BIRC3). Efforts have been made to combine variables into prognostic indices; however, none has been universally adopted. Although a unifying model for all groups of patients and in all situations is appealing, this may prove difficult to attain. Alternatively, focused efforts on patient subgroups in the same clinical context and at certain clinically relevant 'decision points', that is at diagnosis and at initiation of first-line or subsequent treatments, may provide a more accurate approach. In this review, we discuss the advantages and disadvantages as well as the clinical applicability of three recently proposed prognostic models, the MD Anderson nomogram, the integrated cytogenetic and mutational model and the CLL-international prognostic index. We also consider future directions taking into account novel aspects of the disease, such as the tumour microenvironment and the dynamics of (sub)clonal evolution. These aspects are particularly relevant in view of the increasing number of new targeted therapies that have recently emerged.
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Keck School researchers identify differences in colorectal cancer risk among Latino subgroups
Keck School of Medicine of USC - Research News
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Interaction between red meat intake and NAT2 genotype in increasing the risk of colorectal cancer in Japanese and African Americans
PLOS ONE
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Expression and clinical implication of S100A12 in gastric carcinoma
Tumor Biology
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Food-specific response inhibition, dietary restraint and snack intake in lean and overweight/obese adults: A moderated-mediation model
International Journal of Obesity
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BAG3-mediated miRNA let-7g and let-7i inhibit proliferation and enhance apoptosis of human esophageal carcinoma cells by targeting the drug transporter ABCC10
Cancer Letters
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The Toronto Consensus statements for the management of IBD in pregnancy
Gastroenterology
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FAM172A is a tumor suppressor in colorectal carcinoma
Tumor Biology
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Flavones induce immunomodulatory and anti-inflammatory effects by activating cellular anti-oxidant activity: a structure-activity relationship study
Tumor Biology
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Design of a dietary intervention to assess the impact of a gluten-free diet in a population with type 1 Diabetes and Celiac Disease
BMC Gastroenterology
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Capecitabine with/without mitomycin C: results of a randomized phase II trial of second-line therapy in advanced biliary tract adenocarcinoma
Cancer Chemotherapy and Pharmacology
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Combination of miR-125b and miR-27a enhances sensitivity and specificity of AFP-based diagnosis of hepatocellular carcinoma
Tumor Biology
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MicroRNA-122 confers sorafenib resistance to hepatocellular carcinoma cells by targeting IGF-1R to regulate RAS/RAF/ERK signaling pathways
Cancer Letters
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Genetic variants in IL-6/JAK/STAT3 pathway and the risk of CRC
Tumor Biology
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Association between hepatitis B virus infection and risk of multiple myeloma: A systematic review and meta-analysis
Internal Medicine Journal
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
