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1.
Heliyon ; 10(7): e28594, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38617939

RESUMEN

Ions are formed during the combustion process in internal combustion engines. The measurement of ions inside the combustion chamber produces reliable information about the combustion process. The present study focuses on the formation of ions inside the combustion chamber of diesel engines with different injection timing. For this purpose, a multi-zone thermodynamic model is utilized to simulate the closed cycle of the engine. To understand the kinetic behavior of the ions, the model is connected to an ionic chemical kinetics mechanism with 336 reactions and 81 species. Six important ionic reactions comprising 5 ions are used in the ionic mechanism. Dvode differential equation solver is also employed to calculate the energy and kinetics equations. The developed model has an acceptable accuracy in predicting the performance and pollutants of diesel engines. Based on the results, the ion formation is delayed by delaying the fuel injection timing. The maximum amount of in-cylinder ions depends on injection timing. In-cylinder ion current can predict the start of combustion accurately.

2.
Food Chem ; 442: 138619, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38306765

RESUMEN

The growth of plant-based food and drink substitutes has led to increased interest in oat-based milk substitute as a dairy milk alternative. Conventional liquid oat base (LOB) production results in a fibre-rich insoluble by-product and loss of valuable macronutrients. This study investigates the use of xylanase enzymes to release insoluble arabinoxylan (AX) fibre and employs different degrees of milling in the LOB manufacturing process, with the aim to reduce insoluble waste and simultaneously increase soluble dietary fibre in oat-based milk substitutes. The combination of decreased mill gap space from 1 to 0.05 mm and addition of GH10 xylanase, resulted in a homogenous LOB product and solubilization of all available AX. Potential prebiotic arabinoxylooligosaccharides of DP3-7 from GH10 hydrolysis were identified using HPAEC-PAD and MS analysis. These findings demonstrate the value of utilizing xylanases and fine-milling in LOB manufacturing, offering a sustainable approach to maximize health benefits of oat-based beverages.


Asunto(s)
Avena , Endo-1,4-beta Xilanasas , Xilanos , Prebióticos , Bebidas , Nutrientes
3.
Sci Rep ; 14(1): 1163, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38216707

RESUMEN

In this study, a split-type photocatalytic membrane reactor (PMR), incorporating suspended graphitic carbon nitride (g-C3N4) as photocatalyst and a layered polymeric composite (using polyamide, polyethersulfone and polysulfone polymers) as a membrane was fabricated to remove tetracycline (TC) from aqueous solutions as the world's second most used and discharged antibiotic in wastewater. The photocatalyst was synthesised from melamine by ultrasonic-assisted thermal polymerisation method and, along with the membrane, was characterised using various methods, including Brunauer-Emmett-Teller analysis (BET), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), Field emission scanning electron microscopy (FESEM), and Ultraviolet-visible spectroscopy (UV-Vis). The PMR process was optimised, using Design-Expert software for tetracycline removal in terms of UV irradiation time, pH, photocatalyst loading, tetracycline concentration, and membrane separation iteration. It was revealed that a membrane-integrated reactor as a sustainable system could effectively produce clean water by simultaneous removal of tetracycline and photocatalyst from aqueous solution. The maximum removal of 94.8% was obtained at the tetracycline concentration of 22.16 ppm, pH of 9.78 with 0.56 g/L of photocatalyst in the irradiation time of 113.77 min after six times of passing membrane. The PMR system showed reasonable reusability by about a 25.8% drop in TC removal efficiency after seven cycles at optimal conditions. The outcomes demonstrate the promising performance of the proposed PMR system in tetracycline removal from water and suggest that it can be scaled as an effective approach for a sustainable supply of antibiotic-free clean water.

4.
Int J Mol Sci ; 24(16)2023 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-37628970

RESUMEN

The lysosomal cation channel TMEM175 is a Parkinson's disease-related protein and a promising drug target. Unlike whole-cell automated patch-clamp (APC), lysosomal patch-clamp (LPC) facilitates physiological conditions, but is not yet suitable for high-throughput screening (HTS) applications. Here, we apply solid supported membrane-based electrophysiology (SSME), which enables both direct access to lysosomes and high-throughput electrophysiological recordings. In SSME, ion translocation mediated by TMEM175 is stimulated using a concentration gradient at a resting potential of 0 mV. The concentration-dependent K+ response exhibited an I/c curve with two distinct slopes, indicating the existence of two conducting states. We measured H+ fluxes with a permeability ratio of PH/PK = 48,500, which matches literature findings from patch-clamp studies, validating the SSME approach. Additionally, TMEM175 displayed a high pH dependence. Decreasing cytosolic pH inhibited both K+ and H+ conductivity of TMEM175. Conversely, lysosomal pH and pH gradients did not have major effects on TMEM175. Finally, we developed HTS assays for drug screening and evaluated tool compounds (4-AP, Zn as inhibitors; DCPIB, arachidonic acid, SC-79 as enhancers) using SSME and APC. Additionally, we recorded EC50 data for eight blinded TMEM175 enhancers and compared the results across all three assay technologies, including LPC, discussing their advantages and disadvantages.


Asunto(s)
Electrofisiología Cardíaca , Ensayos Analíticos de Alto Rendimiento , Potenciales de la Membrana , Cationes , Lisosomas
5.
Chemosphere ; 336: 139311, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37356592

RESUMEN

Antibiotic pollution in water is a growing threat to public health and the environment, leading to the spread of antimicrobial-resistant bacteria. While photocatalysis has emerged as a promising technology for removing antibiotics from water, its limited efficiency in the visible light range remains a challenge. In this study, we present a novel method for the photocatalytic degradation of tetracycline, the second most commonly used antibiotic worldwide, using α-Fe2O3/TiO2 nanocomposites synthesized via rapid sonochemical and wet impregnation methods. The nanocomposites were characterised and tested using a range of techniques, including BET, TEM, FTIR, XRD, FESEM, EDS, and UV-Vis. The RSM-CCD method was also used to optimize the degradation process by varying four key variables (initial concentration, photocatalyst quantity, irradiation time, and pH). The resulting optimized conditions achieved a remarkable degradation rate of 97.5%. We also investigated the mechanism of photodegradation and the reusability of the photocatalysts, as well as the effect of light source operating conditions. Overall, the results demonstrate the effectiveness of the proposed approach in degrading tetracycline in water and suggest that it may be a promising, eco-friendly technology for the treatment of water contaminated with antibiotics.


Asunto(s)
Aguas Residuales , Contaminantes Químicos del Agua , Catálisis , Contaminantes Químicos del Agua/efectos de la radiación , Tetraciclina , Antibacterianos , Titanio , Agua
6.
Opt Express ; 31(10): 16645-16658, 2023 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-37157740

RESUMEN

Considering the widespread applications of resonant phenomena in metasurfaces to bend, slow, concentrate, guide and manipulate lights, it is important to gain deep analytical insight into different types of resonances. Fano resonance and its special case electromagnetically induced transparency (EIT) which are realized in coupled resonators, have been the subject of many studies due to their high-quality factor and strong field confinement. In this paper, an efficient approach based on Floquet modal expansion is presented to accurately predict the electromagnetic response of two-dimensional/one-dimensional Fano resonant plasmonic metasurfaces. Unlike the previously reported methods, this method is valid over a wide frequency range for different types of coupled resonators and can be applied to practical structures where the array is placed on one or more dielectric layers. Given that the formulation is written in a comprehensive and flexible way, both metal-based and graphene-based plasmonic metasurfaces under normal/oblique incident waves are investigated, and it is demonstrated that this method can be posed as an accurate tool for the design of diverse practical tunable/untunable metasurfaces.

7.
Waste Biomass Valorization ; : 1-11, 2023 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-36713934

RESUMEN

Abstract: Alternative sweeteners, such as steviol glucosides from the plant Stevia rebaudiana Bertoni, are becoming increasingly popular for the design of next-generation foodstuffs. However, the bitter aftertaste of native steviol glucosides is one of the main reasons behind consumer reluctance towards stevia-containing products. Biocatalysis could be a sustainable solution to this problem, through addition of glucosyl moieties to the molecule. Glycoside hydrolases are enzymes performing transglycosylation reactions, and they can be exploited for such modifications. In the present work, the commercial ß-glucanase Finizym 250L® was employed for the transglycosylation of stevioside. After optimization of several reaction parameters, the maximal reaction yield obtained was 19%, with barley ß-glucan as the glycosyl donor. With the aim to develop a sustainable process, ß-glucan extracts from different fungal sources were prepared. Pulsed Electric Field pretreatment of mycelial biomass resulted in extracts with higher ß-glucan content. The extracts were tested as alternative glucosyl donors, reaching up to 15.5% conversion yield, from Pleurotus-extracted ß-glucan. Overall, in the present work a novel enzymatic process for the modification of stevioside is proposed, with concomitant valorization of ß-glucans extracted from fungal biomass, potentially generated as a byproduct from other applications, in concert with the principles of circular economy.

8.
EMBO J ; 41(22): e110963, 2022 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-36217825

RESUMEN

Autophagy provides nutrients during starvation and eliminates detrimental cellular components. However, accumulating evidence indicates that autophagy is not merely a housekeeping process. Here, by combining mouse models of neuron-specific ATG5 deficiency in either excitatory or inhibitory neurons with quantitative proteomics, high-content microscopy, and live-imaging approaches, we show that autophagy protein ATG5 functions in neurons to regulate cAMP-dependent protein kinase A (PKA)-mediated phosphorylation of a synapse-confined proteome. This function of ATG5 is independent of bulk turnover of synaptic proteins and requires the targeting of PKA inhibitory R1 subunits to autophagosomes. Neuronal loss of ATG5 causes synaptic accumulation of PKA-R1, which sequesters the PKA catalytic subunit and diminishes cAMP/PKA-dependent phosphorylation of postsynaptic cytoskeletal proteins that mediate AMPAR trafficking. Furthermore, ATG5 deletion in glutamatergic neurons augments AMPAR-dependent excitatory neurotransmission and causes the appearance of spontaneous recurrent seizures in mice. Our findings identify a novel role of autophagy in regulating PKA signaling at glutamatergic synapses and suggest the PKA as a target for restoration of synaptic function in neurodegenerative conditions with autophagy dysfunction.


Asunto(s)
Neuronas , Sinapsis , Ratones , Animales , Sinapsis/metabolismo , Neuronas/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Transducción de Señal , Autofagia
9.
Cell J ; 24(9): 515-521, 2022 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-36274204

RESUMEN

OBJECTIVE: Recently, development of multifunctional contrast agent for effective targeted molecular computed tomography (CT) imaging of cancer cells stays a major problem. In this study, we explain the ability of Triptorelin peptide-targeted multifunctional bismuth nanoparticles (Bi2S3@ BSA-Triptorelin NPs) for molecular CT imaging. MATERIALS AND METHODS: In this experimental study, the formed nanocomplex of Bi2S3@ BSA-Triptorelin NPs was characterized using different methods. The MTT cytotoxicity test was performed to determine the appropriate concentration of nanoparticles in the MCF-7 cells. The X-ray attenuation intensity and Contrast to Noise Ratio (CNR) of targeted and non-targeted nanoparticles were measured at the concentrations of 25, 50, and 75 µg/ml and X-ray tube voltages of 90, 120 and 140 kVp. RESULTS: We showed that the formed Bi2S3@ BSA-Triptorelin NPs with a Bi core size of approximately ~8.6 nm are nontoxic in a given concentration (0-200 µg/ml). At 90, 120, and 140 tube potentials (kVp), the X-ray attenuation of targeted cells were 1.35, 1.36, and 1.33-times, respectively, more than non-targeted MCF-7cells at the concentration of 75 µg/ml. The CNR values at 90, 120, and 140 kVp tube potentials were 171.5, 153.8 and 146.3 c/Ï­, respectively. CONCLUSION: These findings propose that the diagnostic nanocomplex of Bi2S3@ BSA-Triptorelin NPs can be applied as a good contrast medium for molecular CT techniques.

10.
J Exp Clin Cancer Res ; 41(1): 278, 2022 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-36114510

RESUMEN

Epithelial-mesenchymal transition (EMT) is a fundamental process for embryonic development during which epithelial cells acquire mesenchymal characteristics, and the underlying mechanisms confer malignant features to carcinoma cells such as dissemination throughout the organism and resistance to anticancer treatments. During the past decades, an entire class of molecules, called non-coding RNA (ncRNA), has been characterized as a key regulator of almost every cellular process, including EMT. Like protein-coding genes, ncRNAs can be deregulated in cancer, acting as oncogenes or tumor suppressors. The various forms of ncRNAs, including microRNAs, PIWI-interacting RNAs, small nucleolar RNAs, transfer RNA-derived RNA fragments, long non-coding RNAs, and circular RNAs can orchestrate the complex regulatory networks of EMT at multiple levels. Understanding the molecular mechanism underlying ncRNAs in EMT can provide fundamental insights into cancer metastasis and may lead to novel therapeutic approaches. In this review, we describe recent advances in the understanding of ncRNAs in EMT and provide an overview of recent ncRNA applications in the clinic.


Asunto(s)
MicroARNs , Neoplasias , Transición Epitelial-Mesenquimal/genética , Humanos , MicroARNs/genética , Neoplasias/genética , Neoplasias/patología , ARN Circular , ARN no Traducido/genética
11.
BMC Res Notes ; 14(1): 330, 2021 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-34446103

RESUMEN

OBJECTIVE: Klebsiella pneumoniae is one of most opportunistic pathogens that can be related to nosocomial infections. Increased acquisitions of multidrug resistance in this bacterium as well as the transfer of genes to other strains have caused concern. Integrons play key role in the acquisition and the spread of resistance genes. The aim of this study was evaluated the frequency of resistance genes sulI, sulII, tetA, tetB, class I (intI gene), class II integrons (intII gene) and the association between multidrug resistance and the presence of integrons in K. pneumoniae. RESULTS: Antibiotics susceptibility test was performed on 126 of K. pneumoniae isolates. Also, DNA extraction was done and genes were detected using PCR method. In this study, 67 isolates (53%), carrying both the sulI and sulII genes. Forty-five percent tetracycline-resistant isolates were tetA or tetB positive. The prevalence of intI gene was 96%, while only sixteen isolate harboring intII gene (12.5%). Our results showed the high prevalence of integrons in MDR K. pneumoniae, indicating the important role of these genes in the transmission of antibiotic resistance.


Asunto(s)
Infección Hospitalaria , Infecciones por Klebsiella , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Humanos , Integrones/genética , Irán/epidemiología , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae/genética , Pruebas de Sensibilidad Microbiana
12.
Artículo en Inglés | MEDLINE | ID: mdl-33638084

RESUMEN

This paper aims to investigate the role of water in the reduction of diesel exhaust emissions. To do so, a multi-zone thermodynamic model coupled to a novel semi-detailed ionic chemical kinetics mechanism is used. This mechanism includes 467 reactions and 105 species containing 51 ionic reactions and 15 ions. The mechanism contains 6 basic ionic reactions, 23 NOx-related ionic reactions, and 22 soot-related ionic reactions. Four different amounts of water are added to the in-cylinder mixture and the effects of water in the formation of soot and NOx are investigated. The results showed that water does not have a regular effect on diesel exhaust soot, but causes a significant reduction in exhaust NOx. Water has decreased the temperature of the combustion chamber and consequently has reduced the ionic current inside the combustion chamber. Reduction of the in-cylinder ion current decreases the mass of NOx-related ions and results in reduced exhaust NOx. Adding 5% water reduces the in-cylinder ion current by 47%. Five percent water also reduces engine exhaust NOx to 33%. Among NOx-related ions, water has the greatest effect on N+ ions and reduces its amount to less than 20%. Water affects the progress rate of ionic reactions, and 5% of water reduces the progress rate of the fastest reaction to 14% of its initial value.

13.
Antioxid Redox Signal ; 34(16): 1260-1279, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-32977733

RESUMEN

Aims: Delphinidin (DEL) is a plant-derived antioxidant with clinical potential to treat inflammatory pain but suffers from poor solubility and low bioavailability. The aim of the study was to develop a well-tolerated cyclodextrin (CD)-DEL complex with enhanced bioavailability and to investigate the mechanisms behind its antinociceptive effects in a preclinical model of inflammatory pain. Results: CD-DEL was highly soluble and stable in aqueous solution, and was nontoxic. Systemic administration of CD-DEL reversed mechanical and heat hyperalgesia, while its local application into the complete Freund's adjuvant (CFA)-induced inflamed paw dose-dependently reduced mechanical hyperalgesia, paw volume, formation of the lipid peroxidation product 4-hydroxy-2-nonenal (4-HNE), and tissue migration of CD68+ macrophages. CD-DEL also directly prevented 4-HNE-induced mechanical hyperalgesia, cold allodynia, and an increase in the intracellular calcium concentration into transient receptor potential ankyrin 1 expressing cells. Both 4-HNE- and CFA-induced reactive oxygen species (ROS) levels were sensitive to CD-DEL, while its capacity to scavenge superoxide anion radicals (inhibitory concentration 50 [IC50]: 70 ± 5 µM) was higher than that observed for hydroxyl radicals (IC50: 600 ± 50 µM). Finally, CD-DEL upregulated heme oxygenase 1 that was prevented by HMOX-1 siRNA in vitro. Innovation:In vivo application of DEL to treat inflammatory pain is facilitated by complexation with CD. Apart from its antioxidant effects, the CD-DEL has a unique second antioxidative mechanism involving capturing of 4-HNE into the CD cavity followed by displacement and release of the ROS scavenger DEL. Conclusion: CD-DEL has antinociceptive, antioxidative, and anti-inflammatory effects making it a promising formulation for the local treatment of inflammatory pain.


Asunto(s)
Antocianinas/administración & dosificación , Antiinflamatorios/administración & dosificación , Hiperalgesia/tratamiento farmacológico , beta-Ciclodextrinas/química , Aldehídos/metabolismo , Animales , Antocianinas/química , Antocianinas/farmacología , Antiinflamatorios/química , Antiinflamatorios/farmacología , Calcio/metabolismo , Modelos Animales de Enfermedad , Estabilidad de Medicamentos , Adyuvante de Freund/efectos adversos , Células HEK293 , Humanos , Hiperalgesia/inducido químicamente , Hiperalgesia/metabolismo , Masculino , Ratas , Canal Catiónico TRPA1/genética , Canal Catiónico TRPA1/metabolismo
14.
Environ Pollut ; 266(Pt 2): 115347, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32814177

RESUMEN

The main purpose of current study is accurate prediction of NOx emissions from diesel engines considering in-cylinder ion current. To reach this goal, a validated thermodynamic multi-zone model was used. A modified chemical kinetics mechanism of diesel fuel oxidation was used too. A chemical kinetics mechanism of NOX formation including 103 reactions was added to the main mechanism. A set of ions and ionic reactions was added to the developed chemical kinetics mechanism and finally a modified chemical kinetics mechanism with 445 reactions and 100 species was formed. The developed mechanism was coupled to the multi-zone model and a diesel engine was simulated. The importance of Zeldovich mechanism, prompt mechanism, N2O mechanism and NNH mechanism were investigated. The progress rates of reactions were calculated and important reactions were identified. The results show that the oxygenated ions, NO+, O+ and O2+, has more effects on NO production than other ions. The prompt mechanism plays an important role in predicting the ion current inside the chamber. Because this mechanism has reactions that can lead to CH production. The CH radicals produced by this mechanism can be employed by basic ionic reactions and lead to ion production. The results show that using NOx related ionic reactions results in accurate prediction of engine exhaust NOx.


Asunto(s)
Óxidos de Nitrógeno/análisis , Emisiones de Vehículos , Gasolina
16.
Reprod Health ; 16(1): 108, 2019 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-31315629

RESUMEN

BACKGROUND: Adherence to therapy is a key predictor of the success of human immunodeficiency virus (HIV) treatment. There is limited information available from Iran about that and there is a need for more knowledge about factors influencing treatment adherence. The aim of this study is to examine adherence levels and to explore patients' views about barriers and facilitators to HIV treatment adherence. METHODS: This mixed-method study with the sequential explanatory design has two phases. The first phase (quantitative phase) is a cross- sectional study to assess the in Tabriz, the sixth large city of Iran. A convenience sampling method will be used to select 150 HIV positive patients who visit health centers in Tabriz. The second phase is a qualitative study designed to explore the HIV positive patients' views of barriers and facilitators that can affect their adherence to therapy. In this phase, purposive sampling and in-depth individual interviews will be conducted for data collection. The conventional content analysis approach will be employed for data analysis. In addition to literature review and nominal group technique, the findings of the qualitative and quantitative phases, will be used to recommend some strategies to support adherence to therapy in HIV positive patients. DISCUSSION: This is the first study looking into adherence to therapy and exploring of factors influencing in HIV positive patients which will be performed via a mixed-method approach, aiming to develop health practices improvement strategies. It is worth noting that there is no strategic guideline in Iran's health system for improvement of treatment adherence in HIV positive patients. Health professionals and policy makers can be aware of factors influencing HIV treatment adherence. Therefore, it is hoped that the strategy proposed in the current study can lead to improvements their ability to treatment adherence.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/psicología , Seropositividad para VIH , VIH/aislamiento & purificación , Conocimientos, Actitudes y Práctica en Salud , Cumplimiento de la Medicación/estadística & datos numéricos , Adolescente , Estudios Transversales , Infecciones por VIH/epidemiología , Humanos , Irán/epidemiología , Cumplimiento de la Medicación/psicología , Investigación Cualitativa
18.
Front Mol Neurosci ; 11: 7, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29410612

RESUMEN

Oxidized phospholipids (OxPL) like oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) were recently identified as novel proalgesic targets in acute and chronic inflammatory pain. These endogenous chemical irritants are generated in inflamed tissue and mediate their pain-inducing function by activating the transient receptor potential channels TRPA1 and TRPV1 expressed in sensory neurons. Notably, prototypical therapeutics interfering with OxPL were shown to inhibit TRP channel activation and pain behavior. Here, we asked how OxPL excite primary sensory neurons of dorsal root ganglia (DRG neurons from mice of either sex). Acute stimulation of sensory neurons with the prototypical OxPL 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC) evoked repetitive calcium spikes in small-diameter neurons. As NaV1.9, a voltage-gated sodium channel involved in nociceptor excitability, was previously shown to be essential for the generation of calcium spikes in motoneurons, we asked if this channel is also important for OxPL mediated calcium spike and action potential generation in nociceptors. In wild-type and NaV1.9-deficient neurons, the action potential firing rate and the calcium spike frequency to an acute PGPC stimulus was similar. When preincubated with inflammatory mediators, both, the action potential firing rate and the calcium spike frequency were markedly increased in response to an acute PGPC stimulus. However, this potentiating effect was completely lost in NaV1.9-deficient small-diameter neurons. After treatment with inflammatory mediators, the resting membrane potential of NaV1.9 KO neurons was slightly more negative than that of wild-type control neurons. This suggests that NaV1.9 channels are active under this condition and therefore increases the ease with which action potentials are elicited after OxPL stimulation. In summary, our data suggest that NaV1.9 has a switch function to potentiate the receptor potentials induced by OxPL under inflammatory conditions. Since human NaV1.9 has been shown to mediate painful and painless channelopathies, this study provides new insights into the mechanism by which NaV1.9 amplifies stimuli of endogenous irritants under inflammatory conditions.

19.
Front Mol Neurosci ; 10: 242, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28824373

RESUMEN

Antinociceptive pathways are activated in the periphery in inflammatory pain, for instance resolvins and opioid peptides. Resolvins are biosynthesized from omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid. Resolvin D1 (RvD1) and resolvin E1 (RvE1) initiate the resolution of inflammation and control of hypersensitivity via induction of anti-inflammatory signaling cascades. RvD1 binds to lipoxin A4/annexin-A1 receptor/formyl-peptide receptor 2 (ALX/FPR2), RvE1 to chemerin receptor 23 (ChemR23). Antinociception of RvD1 is mediated by interaction with transient receptor potential channels ankyrin 1 (TRPA1). Endogenous opioid peptides are synthesized and released from leukocytes in the tissue and bind to opioid receptors on nociceptor terminals. Here, we further explored peripheral mechanisms of RvD1 and chemerin (Chem), the ligand of ChemR23, in complete Freund's adjuvant (CFA)-induced hindpaw inflammation in male Wistar rats. RvD1 and Chem ameliorated CFA-induced hypersensitivity in early and late inflammatory phases. This was prevented by peripheral blockade of the µ-opioid peptide receptor (MOR) using low dose local naloxone or by local injection of anti-ß-endorphin and anti-met-enkephalin (anti-ENK) antibodies. Naloxone also hindered antinociception by the TRPA1 inhibitor HC-030031. RvD1 did not stimulate the release of ß-endorphin from macrophages and neutrophils, nor did RvD1 itself activate G-proteins coupled MOR or initiate ß-arrestin recruitment to the membrane. TRPA1 blockade by HC-030031 in inflammation in vivo as well as inhibition of the TRPA1-mediated calcium influx in dorsal root ganglia neurons in vitro was hampered by naloxone. Peripheral application of naloxone alone in vivo already lowered mechanical nociceptive thresholds. Therefore, either a perturbation of the balance of endogenous pro- and antinociceptive mechanisms in early and late inflammation, or an interaction of TRPA1 and opioid receptors weaken the antinociceptive potency of RvD1 and TRPA1 blockers.

20.
Sci Rep ; 7(1): 5447, 2017 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-28710476

RESUMEN

Phospholipids occurring in cell membranes and lipoproteins are converted into oxidized phospholipids (OxPL) by oxidative stress promoting atherosclerotic plaque formation. Here, OxPL were characterized as novel targets in acute and chronic inflammatory pain. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) and its derivatives were identified in inflamed tissue by mass spectrometry and binding assays. They elicited calcium influx, hyperalgesia and induced pro-nociceptive peptide release. Genetic, pharmacological and mass spectrometric evidence in vivo as well as in vitro confirmed the role of transient receptor potential channels (TRPA1 and TRPV1) as OxPAPC targets. Treatment with the monoclonal antibody E06 or with apolipoprotein A-I mimetic peptide D-4F, capturing OxPAPC in atherosclerosis, prevented inflammatory hyperalgesia, and in vitro TRPA1 activation. Administration of D-4F or E06 to rats profoundly ameliorated mechanical hyperalgesia and inflammation in collagen-induced arthritis. These data reveal a clinically relevant role for OxPAPC in inflammation offering therapy for acute and chronic inflammatory pain treatment by scavenging OxPAPC.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Apolipoproteína A-I/farmacología , Artritis Experimental/tratamiento farmacológico , Hiperalgesia/tratamiento farmacológico , Dolor/tratamiento farmacológico , Fosfatidilcolinas/antagonistas & inhibidores , Canal Catiónico TRPA1/genética , Canales Catiónicos TRPV/genética , Animales , Artritis Experimental/inducido químicamente , Artritis Experimental/metabolismo , Artritis Experimental/patología , Calcio/metabolismo , Señalización del Calcio/efectos de los fármacos , Colágeno Tipo II/administración & dosificación , Femenino , Expresión Génica , Células HEK293 , Miembro Posterior , Humanos , Hiperalgesia/inducido químicamente , Hiperalgesia/metabolismo , Hiperalgesia/patología , Masculino , Nocicepción/efectos de los fármacos , Nocicepción/fisiología , Dolor/inducido químicamente , Dolor/metabolismo , Dolor/patología , Técnicas de Placa-Clamp , Fosfatidilcolinas/metabolismo , Fosfatidilcolinas/farmacología , Ratas , Ratas Endogámicas Lew , Ratas Wistar , Canal Catiónico TRPA1/antagonistas & inhibidores , Canal Catiónico TRPA1/metabolismo , Canales Catiónicos TRPV/antagonistas & inhibidores , Canales Catiónicos TRPV/metabolismo
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