TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors; 35681486

Irritable bowel syndrome (IBS) is a chronic functional bowel disorder characterized by intestinal dysmotility. Changes in intestinal microbiota (dysbiosis) can lead to alterations in neuro-muscular functions in the gut. Toll-like receptors (TLRs) 2 and 4 recognize intestinal bacteria and are involved in the motor response induced by gastrointestinal (GI) neurotransmitters. Acetylcholine (ACh) is a well-known neurotransmitter involved in the regulation of GI motility. This study aimed to evaluate the role of TLR2 and TLR4 in the intestinal motor-response induced by ACh in the mouse ileum, as well as the expression and function of the muscarinic and nicotinic ACh receptors. Muscle contractility studies showed that the contractions induced by ACh were significantly lower in TLR2-/- and TLR4-/- with respect to WT mice. In WT mice, the contractions induced by ACh were reduced in the presence of AF-DX AF-DX 116 (a muscarinic ACh receptor (mAChR) M2 antagonist), 4-DAMP (a mAChR M3 antagonist), mecamylamine (a nicotinic AChR receptor (nAChR) a3ß4 antagonist) and a-bungarotoxin (a nAChR a7 antagonist). In TLR2-/- mice, the contractions induced by ACh were increased by AF-DX 116 and mecamylamine. In TLR4-/- mice, the contractions induced by ACh were reduced by a-bungarotoxin and 4-DAMP. The mRNA and protein expressions of M3 and a3 receptors were diminished in the ileum from TLR2-/- and TLR4-/- with respect to WT mice. However, the levels of mRNA and protein of ß4 were diminished only in TLR4-/- but not in TLR2-/- mice. In conclusion, our results show that TLR2 and TLR4 modulates the motor responses to ACh in the mouse ileum. TLR2 acts on muscarinic M2 and M3 and nicotinic a3ß4 ACh receptors, while TLR4 acts on muscarinic M3 and nicotinic a3ß4 and a7 ACh receptors

Selective anticancer and antimicrobial metallodrugs based on Gold(III) dithiocarbamate complexes

New dithiocarbamate cycloaurated complexes have been synthesized and their physicochemical and in vitro antitumor properties have been evaluated. All the performed studies highlighted good transport through the blood and biodistribution, according to the balance between the properties of hydrophilicity/lipophilicity and the binding of moderate strength to the BSA protein. Furthermore, none of the complexes exhibited reduction or decomposition reactions, presenting excellent physiological stability. The in vitro cytotoxic effect was evaluated on human colon cancer cell line Caco-2/TC7, and the complexes showed great antiproliferative activity and excellent selectivity, as much less effect was detected on normal Caco-2/TC7 cells. Most of the complexes exhibit antiproliferative activity that was better than or similar to auranofin, and at least nine times better than that of cisplatin. Its action mechanism is still under discussion since no evidence of cell cycle arrest was found, but an antioxidant role was shown for some of the selective complexes. All complexes were also tested as antimicrobial drugs, exhibiting good activity towards S. aureus and E. coli. bacteria and C. albicans and C. neoformans fungi. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/)

Toll-like receptor 2 modulates the inhibitory motor response induced by hydrogen sulphide in mouse colon

Introduction: The recognition of intestinal microbiota is in part carried out by toll-like receptors (TLR), which are responsible for initiating the innate immune response. Alterations in the intestinal microbiota and its recognition may contribute to the development of intestinal inflammatory pathologies. Otherwise, hydrogen sulphide (H2S) is an endogenous gaseous signalling molecule and it potentially plays a relevant role in the intestinal motility. In mammals, two pyridoxalphosphate-dependent enzymes are responsible for H2S synthesis: cystathionine b-synthase (CBS) and cystathionine -lyase (CSE)..

Development of Suitable CuO-Based Materials Supported on Al2O3, MgAl2O4, and ZrO2 for Ca/Cu H2 Production Process

Functional materials for the sorption enhanced reforming process for H2 production coupled to a Cu/CuO chemical loop have been synthesized. The performance of CuO-based materials supported on Al2O3, MgAl2O4, and ZrO2 and synthesized by different routes has been analyzed. Highly stable materials supported on Al2O3 or MgAl2O4 synthesized by coprecipitation and mechanical mixing with sufficient Cu loads (around 65% wt) have been successfully developed. However, it has been found that coprecipitation under these conditions is not a suitable route for ZrO2. Spray-drying and deposition precipitation did not provide the best chemical features to the materials. As the Ca/Cu process is operated in fixed bed reactors, the best candidates were pelletized and their stability was again assessed. Pellets with high chemical and mechanical stability, high oxygen transport capacity, and good mechanical properties have been finally obtained by coprecipitation. The good homogeneity that provides this route would allow an easy scaling up

Recursive internetwork architecture, investigating RINA as an alternative to TCP/IP (IRATI)

Driven by the requirements of the emerging applications and networks, the Internet has become an architectural patchwork of growing complexity which strains to cope with the changes. Moore’s law prevented us from recognising that the problem does not hide in the high demands of today’s applications but lies in the flaws of the Internet’s original design. The Internet needs to move beyond TCP/IP to prosper in the long term, TCP/IP has outlived its usefulness. The Recursive InterNetwork Architecture (RINA) is a new Internetwork architecture whose fundamental principle is that networking is only interprocess communication (IPC). RINA reconstructs the overall structure of the Internet, forming a model that comprises a single repeating layer, the DIF (Distributed IPC Facility), which is the minimal set of components required to allow distributed IPC between application processes. RINA supports inherently and without the need of extra mechanisms mobility, multi-homing and Quality of Service, provides a secure and configurable environment, motivates for a more competitive marketplace and allows for a seamless adoption. RINA is the best choice for the next generation networks due to its sound theory, simplicity and the features it enables. IRATI’s goal is to achieve further exploration of this new architecture. IRATI will advance the state of the art of RINA towards an architecture reference model and specifcations that are closer to enable implementations deployable in production scenarios. The design and implemention of a RINA prototype on top of Ethernet will permit the experimentation and evaluation of RINA in comparison to TCP/IP. IRATI will use the OFELIA testbed to carry on its experimental activities. Both projects will benefit from the collaboration. IRATI will gain access to a large-scale testbed with a controlled network while OFELIA will get a unique use-case to validate the facility: experimentation of a non-IP based Internet

Antispasmodic effects and action mechanism of essential oil of Chrysactinia mexicana A. Gray on rabbit ileum

The Chrysactinia mexicana A. Gray (C. mexicana) plant is used in folk medicine to treat fever and rheumatism; it is used as a diuretic, antispasmodic; and it is used for its aphrodisiac properties. This study investigates the effects of the essential oil of C. mexicana (EOCM) on the contractility of rabbit ileum and the mechanisms of action involved. Muscle contractility studies in vitro in an organ bath to evaluate the response to EOCM were performed in the rabbit ileum. EOCM (1–100 µg·mL-1) reduced the amplitude and area under the curve of spontaneous contractions of the ileum. The contractions induced by carbachol 1 µM, potassium chloride (KCl) 60 mM or Bay K8644 1 µM were reduced by EOCM (30 µg·mL-1). Apamin 1 µM and charybdotoxin 0.01 µM decreased the inhibition induced by EOCM. The d-cAMP 1 µM decreased the inhibition induced by EOCM. l-NNA 10 µM, Rp-8-Br-PET-cGMPS 1 µM, d, l-propargylglycine 2 mM, or aminooxyacetic acid hemihydrochloride 2 mM did not modify the EOCM effect. In conclusion, EOCM induces an antispasmodic effect and could be used in the treatment of intestinal spasms or diarrhea processes. This effect would be mediated by Ca2+, Ca2+-activated K+ channels and cAMP

Gut microbiota in canine idiopathic epilepsy: Effects of disease and treatment

Epilepsy is one of the most common neurological disorders in humans and dogs. The structure and composition of gut microbiome associated to this disorder has not yet been analyzed in depth but there is evidence that suggests a possible influence of gut bacteria in controlling seizures. The aim of this study was to investigate the changes in gut microbiota associated to canine idiopathic epilepsy (IE) and the possible influence of antiepileptic drugs (AEDs) on the modulation of this microbiota. Faecal microbiota composition was analyzed using sequencing of bacterial 16S rRNA gene in a group of healthy controls (n = 12) and a group of epileptic dogs both before (n = 10) and after a 30-day single treatment with phenobarbital or imepitoin (n = 9). Epileptic dogs showed significantly reduced abundance of GABA (Pseudomonadales, Pseudomonadaceae, Pseudomonas and Pseudomona_graminis) and SCFAs-producing bacteria (Peptococcaceae, Ruminococcaceae and Anaerotruncus) as well as bacteria associated with reduced risk for brain disease (Prevotellaceae) than control dogs. The administration of AEDs during 30 days did not modify the gut microbiota composition. These results are expected to contribute to the understanding of canine idiopathic epilepsy and open up the possibility of studying new therapeutic approaches for this disorder, including probiotic intervention to restore gut microbiota in epileptic individuals. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Scientific culture through Final Thesis in bachelor degree

Resúmenes IV Congreso VetDoc de Docencia Veterinaria, León 2017 (6-7 de Julio)[ES] Durante el curso 2015-16 se ha llevado a cabo una experiencia innovadora en la Facultad de Veterinaria de la Universidad de Zaragoza consistente en la realización de dos Trabajos Fin de Grado (TFG) que, manteniendo su objetivo y carácter académico, han contribuido además a difundir las líneas de investigación sobre las que se trabaja en la Facultad, mediante sendos blogs temáticos desarrollados específicamente y de forma complementaria, dentro del ámbito de la divulgación científica

Intestinal Serotonin Transporter Inhibition by Toll-Like Receptor 2 Activation. A Feedback Modulation

This is the final version of the article. Available from Public Library of Science via the DOI in this record.TLR2 is a microbiota recognition receptor that has been described to contribute to intestinal homeostasis and to ameliorate inflammatory intestinal injury. In this context, serotonin (5-HT) has shown to be an essential intestinal physiological neuromodulator that is also involved in intestinal inflammatory diseases. Since the interaction between TLR2 activation and the intestinal serotoninergic system remains non-investigated, our main aim was to analyze the effect of TLR2 on intestinal serotonin transporter (SERT) activity and expression and the intracellular pathways involved. Caco-2/TC7 cells were used to analyze SERT and TLR2 molecular expression and SERT activity by measuring 5-HT uptake. The results showed that apical TLR2 activation inhibits SERT activity in Caco-2/TC7 cells mainly by reducing SERT protein level either in the plasma membrane, after short-term TLR2 activation or in both the plasma membrane and cell lysate, after long-term activation. cAMP/PKA pathway appears to mediate short-term inhibitory effect of TLR2 on SERT; however, p38 MAPK pathway has been shown to be involved in both short- and long-term TLR2 effect. Reciprocally, 5-HT long-term treatment yielded TLR2 down regulation in Caco-2/TC7 cells. Finally, results from in vivo showed an augmented intestinal SERT expression in mice Tlr2-/-, thus confirming our inhibitory effect of TLR2 on intestinal SERT in vitro. The present work infers that TLR2 may act in intestinal pathophysiology, not only by its inherent innate immune role, but also by regulating the intestinal serotoninergic system.This work was funded by grants from the Spanish Ministry of Science and Innovation and the European Regional Development Fund (ERDF/FEDER) (BFU2010-18971), Zaragoza University (UZ2014-BIO-03), European Social Found (ESF) and the Aragon Regional Government (B61) and the Foundation for the Study of Inflammatory Bowel Diseases in Aragón (ARAINF 012/2008). ARAID Foundation supported J.P. (SAF2014-54763-C2-1-R) and E. Layunta is a PhD student fellow from Aragon Regional Government (B022/13). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A numerical approach to analyze the performance of a PEF-Ohmic heating system in microbial inactivation of solid food

Pulsed Electric Fields (PEF) technology has been recently proposed as a new ohmic-heating system for the heat treatment of solid products in short periods (less than 1 min). However, similar to traditional ohmic heating, non-homogeneous distribution of temperature has been observed and cold points appeared in the interphase between the solid treated product and the electrodes, which can limit the technology for assuring food safety for treated solid products. In this investigation, a computational axisymmetric model of a lab-scale PEF system for a solid product (agar cylinder) was developed. This model was used to predict the temperature and the electric field distribution, treatment time, and the microbial inactivation (Salmonella Typhimurium 878) in the solid product after a PEF-ohmic treatment. Using a factorial analysis, a total of 8 process conditions with different settings of applied field strength levels (2.5–3.75 kV/cm), frequencies (100–200 Hz), and initial agar and electrode temperature (40–50°C) were simulated for the agar cylinder in order to identify the effect and optimal values of these parameters, which offer the most temperature homogeneity. The results showed that the initial temperature of the agar and the electrodes was of great importance in achieving the best temperature uniformity, limiting the occurrence of cold points, and therefore, improving the homogeneity in the level of inactivation of Salmonella Typhimurium 878 all over the agar cylinder. A treatment of 2.3 s would be enough at 3.75 kV/cm, 200 Hz with an initial temperature of 50°C of the agar and the electrodes, for a 5-Log10 reduction of Salmonella Typhimurium 878 in the whole product with a deviation of 9°C between the coldest and hottest point of the solid