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Open AccessArticle
Tumour-Secreted Protein S (ProS1) Activates a Tyro3-Erk Signalling Axis and Protects Cancer Cells from Apoptosis
Cancers 2019, 11(12), 1843; https://doi.org/10.3390/cancers11121843 (registering DOI) - 22 Nov 2019
Abstract
The TAM subfamily (Tyro3, Axl, MerTK) of receptor tyrosine kinases are implicated in several cancers, where they have been shown to support primary tumorigenesis as well as secondary resistance to cancer therapies. Relatively little is known about the oncogenic role of Tyro3, including [...] Read more.
The TAM subfamily (Tyro3, Axl, MerTK) of receptor tyrosine kinases are implicated in several cancers, where they have been shown to support primary tumorigenesis as well as secondary resistance to cancer therapies. Relatively little is known about the oncogenic role of Tyro3, including its ligand selectivity and signalling in cancer cells. Tyro3 showed widespread protein and mRNA expression in a variety of human cancer cell lines. In SCC-25 head and neck cancer cells expressing both Tyro3 and Axl, Western blotting showed that both natural TAM ligands ProS1 and Gas6 rapidly stimulated Tyro3 and Erk kinase phosphorylation, with ProS1 eliciting a greater effect. In contrast, Gas6 was the sole stimulator of Axl and Akt kinase phosphorylation. In MGH-U3 bladder cancer cells, which express Tyro3 alone, ProS1 was again the stronger stimulator of Tyro3 and Erk stimulation but additionally stimulated Akt phosphorylation. Conditioned medium from ProS1-secreting 786-0 kidney cancer cells replicated the kinase activation effects of recombinant ProS1 in SCC-25 cells, with specificity confirmed by ProS1 ligand traps and warfarin. In addition, ProS1 protected cancer cells from acute apoptosis induced by staurosporine, as well as additionally, long-term serum starvation-induced apoptosis in MGH-U3 cells (Tyro3 only), which reflects its additional coupling to Akt signalling in these cells. In conclusion, we have shown that ProS1 is a tumour-derived functional ligand for Tyro3 that supports cancer cell survival. Furthermore, the ProS1-Tyro3 interaction is primarily coupled to Erk signalling although it displays signalling diversity dependent upon its representative expression as a TAM receptor in tumour cells. Full article
(This article belongs to the collection Kinases and Cancer)
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Open AccessArticle
Improving the Light-Induced Spin Transition Efficiency in Ni(II)-Based Macrocyclic-Ligand Complexes
Molecules 2019, 24(23), 4249; https://doi.org/10.3390/molecules24234249 (registering DOI) - 22 Nov 2019
Abstract
The structural stability and photoabsorption properties of Ni(II)-based metal-organic complexes with octahedral coordination having different planar ligand ring structures were investigated employing density functional theory (DFT) and its time-dependent extension (TD-DFT) considering the M06 exchange-correlation functional and the Def2-TZVP basis set. The results [...] Read more.
The structural stability and photoabsorption properties of Ni(II)-based metal-organic complexes with octahedral coordination having different planar ligand ring structures were investigated employing density functional theory (DFT) and its time-dependent extension (TD-DFT) considering the M06 exchange-correlation functional and the Def2-TZVP basis set. The results showed that the molecular composition of different planar cyclic ligand structures had significant influences on the structural stability and photoabsorption properties of metal-organic complexes. Only those planar ligands that contained aromatic rings met the basic criteria (thermal stability, structural reversibility, and appropriate excitation frequency domain) for light-induced excited spin state trapping, but their spin transition efficiencies were very different. While, in all three aromatic cases, the singlet electronic excitations induced charge distribution that could help in the singlet-to-triplet spin transition, and triplet excitations, which could assist in the backward (triplet-to-singlet) spin transition, was found only for one complex. Full article
(This article belongs to the Section Computational and Theoretical Chemistry)
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Open AccessHypothesis
pMHC Structural Comparisons as a Pivotal Element to Detect and Validate T-Cell Targets for Vaccine Development and Immunotherapy—A New Methodological Proposal
Cells 2019, 8(12), 1488; https://doi.org/10.3390/cells8121488 (registering DOI) - 22 Nov 2019
Abstract
The search for epitopes that will effectively trigger an immune response remains the “El Dorado” for immunologists. The development of promising immunotherapeutic approaches requires the appropriate targets to elicit a proper immune response. Considering the high degree of HLA/TCR diversity, as well as [...] Read more.
The search for epitopes that will effectively trigger an immune response remains the “El Dorado” for immunologists. The development of promising immunotherapeutic approaches requires the appropriate targets to elicit a proper immune response. Considering the high degree of HLA/TCR diversity, as well as the heterogeneity of viral and tumor proteins, this number will invariably be higher than ideal to test. It is known that the recognition of a peptide-MHC (pMHC) by the T-cell receptor is performed entirely in a structural fashion, where the atomic interactions of both structures, pMHC and TCR, dictate the fate of the process. However, epitopes with a similar composition of amino acids can produce dissimilar surfaces. Conversely, sequences with no conspicuous similarities can exhibit similar TCR interaction surfaces. In the last decade, our group developed a database and in silico structural methods to extract molecular fingerprints that trigger T-cell immune responses, mainly referring to physicochemical similarities, which could explain the immunogenic differences presented by different pMHC-I complexes. Here, we propose an immunoinformatic approach that considers a structural level of information, combined with an experimental technology that simulates the presentation of epitopes for a T cell, to improve vaccine production and immunotherapy efficacy. Full article
(This article belongs to the Section Cellular Immunology)
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Open AccessReview
Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration
Nutrients 2019, 11(12), 2862; https://doi.org/10.3390/nu11122862 (registering DOI) - 22 Nov 2019
Abstract
The human gut is inhabited by trillions of microorganisms composing a dynamic ecosystem implicated in health and disease. The composition of the gut microbiota is unique to each individual and tends to remain relatively stable throughout life, yet daily transient fluctuations are observed. [...] Read more.
The human gut is inhabited by trillions of microorganisms composing a dynamic ecosystem implicated in health and disease. The composition of the gut microbiota is unique to each individual and tends to remain relatively stable throughout life, yet daily transient fluctuations are observed. Diet is a key modifiable factor influencing the composition of the gut microbiota, indicating the potential for therapeutic dietary strategies to manipulate microbial diversity, composition, and stability. While diet can induce a shift in the gut microbiota, these changes appear to be temporary. Whether prolonged dietary changes can induce permanent alterations in the gut microbiota is unknown, mainly due to a lack of long-term human dietary interventions, or long-term follow-ups of short-term dietary interventions. It is possible that habitual diets have a greater influence on the gut microbiota than acute dietary strategies. This review presents the current knowledge around the response of the gut microbiota to short-term and long-term dietary interventions and identifies major factors that contribute to microbiota response to diet. Overall, further research on long-term diets that include health and microbiome measures is required before clinical recommendations can be made for dietary modulation of the gut microbiota for health. Full article
(This article belongs to the Special Issue Dietary Compounds Impact on Human Gut Microbiome and Gut Health)
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Open AccessArticle
Towards a Framework for Noctilucent Cloud Analysis
Remote Sens. 2019, 11(23), 2743; https://doi.org/10.3390/rs11232743 (registering DOI) - 22 Nov 2019
Abstract
In this paper, we present a framework to study the spatial structure of noctilucent clouds formed by ice particles in the upper atmosphere at mid and high latitudes during summer. We studied noctilucent cloud activity in optical images taken from three different locations [...] Read more.
In this paper, we present a framework to study the spatial structure of noctilucent clouds formed by ice particles in the upper atmosphere at mid and high latitudes during summer. We studied noctilucent cloud activity in optical images taken from three different locations and under different atmospheric conditions. In order to identify and distinguish noctilucent cloud activity from other objects in the scene, we employed linear discriminant analysis (LDA) with feature vectors ranging from simple metrics to higher-order local autocorrelation (HLAC), and histogram of oriented gradients (HOG). Finally, we propose a convolutional neural networks (CNN)-based method for the detection of noctilucent clouds. The results clearly indicate that the CNN-based approach outperforms the LDA-based methods used in this article. Furthermore, we outline suggestions for future research directions to establish a framework that can be used for synchronizing the optical observations from ground-based camera systems with echoes measured with radar systems like EISCAT in order to obtain independent additional information on the ice clouds. Full article
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Open AccessProceedings
TI-Stan: Adaptively Annealed Thermodynamic Integration with HMC
Proceedings 2019, 33(1), 9; https://doi.org/10.3390/proceedings2019033009 (registering DOI) - 22 Nov 2019
Abstract
We present a novel implementation of the adaptively annealed thermodynamic integration technique using Hamiltonian Monte Carlo (HMC). Thermodynamic integration with importance sampling and adaptive annealing is an especially useful method for estimating model evidence for problems that use physics-based mathematical models. Because it [...] Read more.
We present a novel implementation of the adaptively annealed thermodynamic integration technique using Hamiltonian Monte Carlo (HMC). Thermodynamic integration with importance sampling and adaptive annealing is an especially useful method for estimating model evidence for problems that use physics-based mathematical models. Because it is based on importance sampling, this method requires an efficient way to refresh the ensemble of samples. Existing successful implementations use binary slice sampling on the Hilbert curve to accomplish this task. This implementation works well if the model has few parameters or if it can be broken into separate parts with identical parameter priors that can be refreshed separately. However, for models that are not separable and have many parameters, a different method for refreshing the samples is needed. HMC, in the form of the MC-Stan package, is effective for jointly refreshing the ensemble under a high-dimensional model. MC-Stan uses automatic differentiation to compute the gradients of the likelihood that HMC requires in about the same amount of time as it computes the likelihood function itself, easing the programming burden compared to implementations of HMC that require explicitly specified gradient functions. We present a description of the overall TI-Stan procedure and results for representative example problems. Full article
Open AccessArticle
High Below-Ground Productivity Allocation of Alpine Grasslands on the Northern Tibet
Plants 2019, 8(12), 535; https://doi.org/10.3390/plants8120535 (registering DOI) - 22 Nov 2019
Abstract
The allocation of net primary production (NPP) between above- and belowground components is a key step of ecosystem material cycling and energy flows, which determines many critical parameters, e.g., the fraction of below ground NPP (BNPP) to NPP (fBNPP) and [...] Read more.
The allocation of net primary production (NPP) between above- and belowground components is a key step of ecosystem material cycling and energy flows, which determines many critical parameters, e.g., the fraction of below ground NPP (BNPP) to NPP (fBNPP) and root turnover rates (RTR), in vegetation models. However, direct NPP estimation and partition are scarcely based on field measurements of biomass dynamics in the alpine grasslands on the Northern Tibetan Plateau (NTP). Consequently, these parameters are unverifiable and controversial. Here, we measured above- and belowground biomass dynamics (monthly from May to September each year from 2013 to 2015) to estimate NPP dynamics and allocations in four typical alpine grassland ecosystems, i.e., an alpine meadow, alpine meadow steppe, alpine steppe and alpine desert steppe. We found that NPP and its components, above and below ground NPP (ANPP and BNPP), increased significantly from west to east on the NTP, and ANPP was mainly affected by temperature while BNPP and NPP were mainly affected by precipitation. The bulk of BNPP was generally concentrated in the top 10 cm soil layers in all four alpine grasslands (76.1% ± 9.1%, mean ± SD). Our results showed that fBNPP was significantly different among these four alpine grasslands, with its means in alpine meadow (0.93), alpine desert steppe (0.92) being larger than that in the alpine meadow steppe (0.76) and alpine steppe (0.77). Both temperature and precipitation had significant and positive effects on the fBNPP, while their interaction effects were significantly opposite. RTR decreased with increasing precipitation, but increased with increasing temperature across this ecoregion. Our study illustrated that alpine grasslands on the NTP, especially in the alpine meadow and alpine desert steppe, partitioned an unexpected and greater NPP to below ground than most historical reports across global grasslands, indicating a more critical role of the root carbon pool in carbon cycling in alpine grasslands on the NTP. Full article
(This article belongs to the Section Plant Ecology)
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Open AccessArticle
Survivability of Anhydrobiotic Cyanobacteria in Salty Ice: Implications for the Habitability of Icy Worlds
Life 2019, 9(4), 86; https://doi.org/10.3390/life9040086 (registering DOI) - 22 Nov 2019
Abstract
Two anhydrobiotic strains of the cyanobacterium Chroococcidiopsis, namely CCMEE 029 and CCMEE 171, isolated from the Negev Desert in Israel and from the Dry Valleys in Antarctica, were exposed to salty-ice simulations. The aim of the experiment was to investigate the cyanobacterial [...] Read more.
Two anhydrobiotic strains of the cyanobacterium Chroococcidiopsis, namely CCMEE 029 and CCMEE 171, isolated from the Negev Desert in Israel and from the Dry Valleys in Antarctica, were exposed to salty-ice simulations. The aim of the experiment was to investigate the cyanobacterial capability to survive under sub-freezing temperatures in samples simulating the environment of icy worlds. The two strains were mixed with liquid solutions having sub-eutectic concentration of Na2SO4, MgSO4 and NaCl, then frozen down to different final temperatures (258 K, 233 K and 203 K) in various experimental runs. Both strains survived the exposure to 258 K in NaCl solution, probably as they migrated in the liquid veins between ice grain boundaries. However, they also survived at 258 K in Na2SO4 and MgSO4-salty-ice samples—that is, a temperature well below the eutectic temperature of the solutions, where liquid veins should not exist anymore. Moreover, both strains survived the exposure at 233 K in each salty-ice sample, with CCMEE 171 showing an enhanced survivability, whereas there were no survivors at 203 K. The survival limit at low temperature was further extended when both strains were exposed to 193 K as air-dried cells. The results suggest that vitrification might be a strategy for microbial life forms to survive in potentially habitable icy moons, for example in Europa’s icy crust. By entering a dried, frozen state, they could be transported from niches, which became non-habitable to new habitable ones, and possibly return to metabolic activity. Full article
(This article belongs to the Special Issue Planetary Exploration of Habitable Environments)
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Open AccessArticle
Perceptions about the Self-Learning Methodology in Simulated Environments in Nursing Students: A Mixed Study
Int. J. Environ. Res. Public Health 2019, 16(23), 4646; https://doi.org/10.3390/ijerph16234646 (registering DOI) - 22 Nov 2019
Abstract
The self-learning methodology in simulated environments (MAES©) is an active method of education. The aim of this study was to analyze the perceptions and opinions of undergraduate and graduate nursing students about the self-learning methodology in simulated environments. A mixed, cross-sectional, descriptive study [...] Read more.
The self-learning methodology in simulated environments (MAES©) is an active method of education. The aim of this study was to analyze the perceptions and opinions of undergraduate and graduate nursing students about the self-learning methodology in simulated environments. A mixed, cross-sectional, descriptive study based on a survey tool made ad hoc (quantitative approach) and an open questionnaire (qualitative approach) was carried out. A sample of 149 undergraduate and 25 postgraduate nursing students were tested. The score was high for all the variables of the questionnaire analyzed: for perception of simulation performance, M = 73.5 (SD = 14.5), for motivation, M = 23.9 (SD = 5.9), for the opinion about facilitators, M = 25.9 (SD = 4.5), and for the promotion of team work, M = 16.9 (SD = 3.4). Five dimensions were identified and evaluated in the qualitative research. The students were pleased with MAES© and had a positive perception, since they considered that MAES© increased their learning. Full article
(This article belongs to the Special Issue Nursing Research)
Open AccessArticle
Use of Fermented Hemp, Chickpea and Milling By-Products to Improve the Nutritional Value of Semolina Pasta
Foods 2019, 8(12), 604; https://doi.org/10.3390/foods8120604 (registering DOI) - 22 Nov 2019
Abstract
A biotechnological approach including enzymatic treatment (protease and xylanase) and lactic acid bacteria fermentation has been evaluated to enhance the nutritional value of semolina pasta enriched with hemp, chickpea and milling by-products. The intense (up to circa, (ca.) 70%) decrease in the peptide [...] Read more.
A biotechnological approach including enzymatic treatment (protease and xylanase) and lactic acid bacteria fermentation has been evaluated to enhance the nutritional value of semolina pasta enriched with hemp, chickpea and milling by-products. The intense (up to circa, (ca.) 70%) decrease in the peptide profile area and (up to two-fold) increase in total free amino acids, compared to the untreated raw materials, highlighted the potential of lactic acid bacteria to positively affect their in vitro protein digestibility. Fermented and unfermented ingredients have been characterized and used to fortify pasta made under pilot-plant scale. Due to the high contents of protein (ca. 13%) and fiber (ca. 6%) and according to the Regulation of the European Community (EC) No. 1924/2006 fortified pasta can be labelled as a “source of fiber” and a “source of protein”. The use of non-wheat flours increased the content of anti-nutritional factors as compared to the control pasta. Nevertheless, fermentation with lactic acid bacteria led to significant decreases in condensed tannins (ca. 50%), phytic acid and raffinose (ca. ten-fold) contents as compared to the unfermented pasta. Moreover, total free amino acids and in vitro protein digestibility values were 60% and 70%, respectively, higher than pasta made only with semolina. Sensory analysis highlighted a strong effect of the fortification on the sensory profile of pasta. Full article
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Open AccessArticle
Synthesis of Sub 3 nm-Sized Uniform Magnetite Nanoparticles Using Reverse Micelle Method for Biomedical Application
Materials 2019, 12(23), 3850; https://doi.org/10.3390/ma12233850 (registering DOI) - 22 Nov 2019
Abstract
We report a synthetic method for small and uniform Fe3O4 (magnetite) nanoparticles under mild conditions. Spherical sub-3 nm-sized magnetite nanoparticles were prepared via reverse micelles composed of oleylamine, F127, xylene, and water for the reaction of iron(III) stearate with hydrazine [...] Read more.
We report a synthetic method for small and uniform Fe3O4 (magnetite) nanoparticles under mild conditions. Spherical sub-3 nm-sized magnetite nanoparticles were prepared via reverse micelles composed of oleylamine, F127, xylene, and water for the reaction of iron(III) stearate with hydrazine at a reaction temperature of 90 °C in air atmosphere. These synthesized magnetite nanoparticles exhibited good size uniformity. By controlling experimental conditions, we could easily control both size and size uniformity of these magnetite nanoparticles. We further investigated whether Fe3O4 could be used in biomedical applications. Cytotoxicity of Fe3O4 was evaluated with human adipose-derived stem cells (hADSCs). Our results showed that the number of hADSCs did not significantly decrease when these cells were treated with Fe3O4 nanoparticles at a concentration of up to 9 μg/mL. Apoptotic activity and cell proliferation of hADSCs treated with Fe3O4 nanoparticles were similar to those of hADSCs without any treatment. This novel method could be used for synthesizing uniform and biocompatible Fe3O4 nanoparticles with further biomedical applications. Full article
(This article belongs to the Special Issue Polymers for Medical Applications)
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Open AccessArticle
3D Bioprinting of Novel Biocompatible Scaffolds for Endothelial Cell Repair
Polymers 2019, 11(12), 1924; https://doi.org/10.3390/polym11121924 (registering DOI) - 22 Nov 2019
Abstract
The aim of this study was to develop and evaluate an optimized 3D bioprinting technology in order to fabricate novel scaffolds for the application of endothelial cell repair. Various biocompatible and biodegradable macroporous scaffolds (D = 10 mm) with interconnected pores (D = [...] Read more.
The aim of this study was to develop and evaluate an optimized 3D bioprinting technology in order to fabricate novel scaffolds for the application of endothelial cell repair. Various biocompatible and biodegradable macroporous scaffolds (D = 10 mm) with interconnected pores (D = ~500 µm) were fabricated using a commercially available 3D bioprinter (r3bEL mini, SE3D, USA). The resolution of the printing layers was set at ~100 µm for all scaffolds. Various compositions of polylactic acid (PLA), polyethylene glycol (PEG) and pluronic F127 (F127) formulations were prepared and optimized to develop semi-solid viscous bioinks. Either dimethyloxalylglycine (DMOG) or erythroprotein (EPO) was used as a model drug and loaded in the viscous biocompatible ink formulations with a final concentration of 30% (w/w). The surface analysis of the bioinks via a spectroscopic analysis revealed a homogenous distribution of the forming materials throughout the surface, whereas SEM imaging of the scaffolds showed a smooth surface with homogenous macro-porous texture and precise pore size. The rheological and mechanical analyses showed optimum rheological and mechanical properties of each scaffold. As the drug, DMOG, is a HIF-1 inducer, its release from the scaffolds into PBS solution was measured indirectly using a bioassay for HIF-1α. This showed that the release of DMOG was sustained over 48 h. The release of DMOG was enough to cause a significant increase in HIF-1α levels in the bioassay, and when incubated with rat aortic endothelial cells (RAECs) for 2 h resulted in transcriptional activation of a HIF-1α target gene (VEGF). The optimum time for the increased expression of VEGF gene was approximately 30 min and was a 3-4-fold increase above baseline. This study provides a proof of concept, that a novel bioprinting platform can be exploited to develop biodegradable composite scaffolds for potential clinical applications in endothelial cell repair in cardiovascular disease (CVD), or in other conditions in which endothelial damage occurs. Full article
(This article belongs to the Special Issue 3D and 4D Printing of (Bio)Materials)
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Open AccessArticle
Properties of Mortar with Recycled Aggregates, and Polyacrylonitrile Microfibers Synthesized by Electrospinning
Materials 2019, 12(23), 3849; https://doi.org/10.3390/ma12233849 (registering DOI) - 22 Nov 2019
Abstract
Currently it is necessary to find alternatives towards a sustainable construction, in order to optimize the management of natural resources. Thus, using recycled fine aggregate (RFA) is a viable recycling option for the production of new cementitious materials. In addition, the use of [...] Read more.
Currently it is necessary to find alternatives towards a sustainable construction, in order to optimize the management of natural resources. Thus, using recycled fine aggregate (RFA) is a viable recycling option for the production of new cementitious materials. In addition, the use of polymeric microfibers would cause an increase in the properties of these materials. In this work, mortars were studied with 25% of RFA and an addition of polyacrylonitrile PAN microfibers of 0.05% in cement weight. The microfibers were obtained by the electrospinning method, which had an average diameter of 1.024 µm and were separated by means of a homogenizer to be added to the mortar. Cementing materials under study were evaluated for compressive strength, flexural strength, total porosity, effective porosity and capillary absorption, resistance to water penetration, sorptivity and carbonation. The results showed that using 25% of RFA causes decreases mechanical properties and durability, but adding PAN microfibers in 0.05% caused an increase of 2.9% and 30.8% of compressive strength and flexural strength respectively (with respect to the reference sample); a decrease in total porosity of 5.8% and effective porosity of 7.4%; and significant decreases in capillary absorption (approximately 23.3%), resistance to water penetration (25%) and carbonation (14.3% after 28 days of exposure). The results showed that the use of PAN microfibers in recycled mortars allowed it to increase the mechanical properties (because they increase the tensile strength), helped to fill pores or cavities and this causes them to be mortars with greater durability. Therefore, the use of PAN microfibers as a reinforcement in recycled cementitious materials would be a viable option to increase their applications. Full article
(This article belongs to the Special Issue Properties and Novel Applications of Recycled Aggregates)
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Open AccessArticle
Meningitic Escherichia coli Induction of ANGPTL4 in Brain Microvascular Endothelial Cells Contributes to Blood–Brain Barrier Disruption via ARHGAP5/RhoA/MYL5 Signaling Cascade
Pathogens 2019, 8(4), 254; https://doi.org/10.3390/pathogens8040254 (registering DOI) - 22 Nov 2019
Abstract
Bacterial meningitis is currently recognized as one of the most important life-threatening infections of the central nervous system (CNS) with high morbidity and mortality, despite the advancements in antimicrobial treatment. The disruption of blood–brain barrier (BBB) induced by meningitis bacteria is crucial for [...] Read more.
Bacterial meningitis is currently recognized as one of the most important life-threatening infections of the central nervous system (CNS) with high morbidity and mortality, despite the advancements in antimicrobial treatment. The disruption of blood–brain barrier (BBB) induced by meningitis bacteria is crucial for the development of bacterial meningitis. However, the complete mechanisms involving in the BBB disruption remain to be elucidated. Here, we found meningitic Escherichia coli induction of angiopoietin-like 4 (ANGPTL4) in brain microvascular endothelial cells (BMECs) contributes to BBB disruption via ARHGAP5/RhoA/MYL5 signaling cascade, by the demonstration that ANGPTL4 was significantly upregulated in meningitis E. coli infection of BMECs as well as mice, and treatment of the recombinant ANGPTL4 protein led to an increased permeability of the BBB in vitro and in vivo. Moreover, we found that ANGPTL4 did not affect the expression of tight junction proteins involved in BBB disruption, but it increased the expression of MYL5, which was found to have a negative role on the regulation of barrier function during meningitic E. coli infection, through the activation of RhoA signaling pathway. To our knowledge, this is the first report demonstrating the disruption of BBB induced by ANGPTL4 through the ARHGAP5/RhoA/MYL5 pathway, which largely supports the involvement of ANGPTL4 during meningitic E. coli invasion and further expands the theoretical basis for the mechanism of bacterial meningitis. Full article
(This article belongs to the Special Issue Pathogenesis of Fungal and Bacterial Microbes)
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