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1.
Chemosphere ; 349: 140820, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38040253

RESUMO

Microwave-induced plasmas generated at atmospheric pressure are very attractive for a great variety of applications since they have a relatively high electron density and can generate large amounts of reactive species. Argon plasmas can be sustained inside dielectric tubes but are radially contracted and exhibit filamentation effects when the diameter of the tube is not narrow enough (over 1.5 mm). In this work, we describe a new approach for creating microwave (2.45 GHz) plasmas under atmospheric pressure conditions by using a surfatron device and power from 10 W. This modified design of the reactor enables the sustenance of non-filamented argon plasmas. These new plasmas have a higher gas temperature and electron density than the plasma generated in the original surfatron configuration. The new design also allows for the maintenance of plasmas with relatively high proportions of water, resulting in the generation of larger quantities of excited hydroxyl radicals (·OH*). Thus, this novel configuration extends the applicability of microwave-induced plasmas by enabling operation under new conditions. Finally, the degradation of methylene blue (MB) in aqueous solutions has been assessed under different initial dye concentrations and argon flow conditions. The new plasma produces a substantial increase in hydrogen peroxide and nitrate concentrations in water and leads to a noteworthy enhancement in MB degradation efficiency. The introduction of water into the plasma produces a minor additional improvement.


Assuntos
Azul de Metileno , Micro-Ondas , Água , Argônio , Peróxido de Hidrogênio
3.
Sci Rep ; 13(1): 14481, 2023 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-37660209

RESUMO

Exercise plays an important role in cardiac health and enhances the transport of glucose in cardiac muscle by increasing the glucose transporter-4 (GLUT4) content at the cell membrane. The GLUT4 gene is a target of myocyte enhancer transcription factor 2A (MEF2A). Several transcription factors are regulated by microRNAs (miRs), small non-coding RNAs that control gene expression at the posttranscriptional level. In this study we tested the hypothesis that exercise regulates the expression of miR-223 and that MEF2A is a direct target of miR-223. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot experiments showed that GLUT4 gene expression and protein abundance increased by 30 and 23%, respectively, in the microsomal fraction immediately after exercise, and had returned to control levels after 18 h. In contrast, the increase in GLUT4 in the membrane fraction was delayed. Exercise also increased the protein abundance of transcription factors involved in GLUT4 expression. Immediately after exercise, the protein abundance of MEF2A, nuclear respiratory factor 1 (NRF1), and forkhead box O1 (FOXO1) increased by 18, 30, and 40%, respectively. qRT-PCR experiments showed that miR-223-3p and miR-223-5p expression decreased immediately after exercise by 60 and 30%, respectively, and luciferase assays indicated that MEF2A is a target of the 5p strand of miR-223. Overexpression of miR-223-5p in H9c2 cells decreased the protein abundance of MEF2A. Our results suggest that the exercise-induced increase in GLUT4 content in cardiac muscle is partly due to the posttranscriptional increase in MEF2A protein abundance caused by the decrease in miR-223-5p expression. The exercise-induced decrease in miR-223-3p expression likely contributes to the increases in NRF1 and FOXO1 abundance and GLUT4 content.


Assuntos
MicroRNAs , Miocárdio , Animais , Ratos , Coração , Bioensaio , Fatores de Transcrição MEF2/genética , MicroRNAs/genética , Fator 1 Nuclear Respiratório
4.
Neurologist ; 27(1): 27-29, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34842572

RESUMO

INTRODUCTION: Myelopathy is a common condition with a variety of causes, often eluding diagnosis for some time. Prolonged flexion after surgical procedures has been described. CASE REPORT: A 20-year-old female presented with acute paraparesis after polysubstance drug intoxication and a period of prolonged neck flexion while unconscious. Imaging demonstrated extensive cervicothoracic central cord signal change, in addition to posterior neck musculature hyperintensity. Additional workup directed to other causes was negative. The patient was diagnosed with flexion myelopathy and was treated with a course of steroids, with marked improvement. CONCLUSIONS: The clinician should consider the possibility of flexion-related myelopathy particularly in cases of drug intoxication or prolonged unconsciousness. Signal change within cervical musculature may provide additional clues and allow diagnosis in a timely manner.


Assuntos
Preparações Farmacêuticas , Doenças da Medula Espinal , Adulto , Vértebras Cervicais , Feminino , Humanos , Imageamento por Ressonância Magnética , Amplitude de Movimento Articular , Doenças da Medula Espinal/induzido quimicamente , Doenças da Medula Espinal/diagnóstico por imagem , Adulto Jovem
5.
Medicina (B Aires) ; 81(4): 536-545, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34453794

RESUMO

Individuals with malignancies and COVID-19 have a lower survival compared with the general population. However, the information about the impact of COVID-19 on the whole hematological population is scarce. We aimed to describe the 30th day overall survival (OS) after COVID-19 infection in patients with a hematological disease in Argentina. A completely anonymous survey from the Argentine Society of Hematology was delivered to all the hematologists in Argentina; it started in April 2020. A cut-off to analyze the data was performed in December 2020 and, finally, 419 patients were reported and suitable for the analysis (average age: 58 years, 90% with malignant diseases). After the COVID-19 diagnosis, the 30-day OS for the whole population was 80.2%. From the entire group (419), 101 (24.1%) individuals required intensive care unit admission, where the 30-day OS was 46.6%. Among allogeneic stem cell transplant recipients, the 30-day OS was 70.3%. Factors associated with a low OS were two or more comorbidities, an active hematological disease and history of chemotherapy. In individuals with the three factors, the 30-day OS was 49.6% while the 30-day OS in those without those factors was 100%. Patients with hematological diseases have a higher mortality than the general population. This group represents a challenge and requires careful decision-making of the treatment in order not to compromise the chances of cure.


El presente estudio tuvo por objetivo primario conocer la mortalidad de pacientes con enfermedad hematológica que presentaron infección por COVID-19 en Argentina. Para ello se difundió una encuesta desde la Sociedad Argentina de Hematología (SAH) entre los hematológos para informar sobre los pacientes con enfermedades hematológicas y diagnóstico de infección por SARS- CoV-2, entre el 19/4/2020, y el 7/12/2020. Se incluyeron individuos de todas las edades con diagnóstico de enfermedad hematológica benigna o maligna e infección por SARS-CoV-2 confirmada por técnica de RTPCR. Se analizaron 419 pacientes (mediana 58 años; 90% enfermedades malignas). La supervivencia al día 30 fue de 80.2%. La supervivencia fue menor en aquellos que requirieron internación (74.2%), cuidados intensivos (46.6%) y asistencia respiratoria mecánica (36.8%). Entre los trasplantados alogénicos la supervivencia fue 70.3%. Los factores vinculados a la supervivencia global fueron las comorbilidades, el estado de la enfermedad al momento de la infección y el antecedente de quimioterapia. Se pudo establecer un score en el que aquellos que tuvieron un puntaje de 4 alcanzaron una supervivencia del 49.6% al día 30, mientras que la de los pacientes con score 0 fue del 100% a 30 días. En comparación con la población general, los pacientes con enfermedades hematológicas presentan una mayor mortalidad vinculada al COVID-19, motivo por el cual es primordial definir pautas destinadas a disminuir la exposición de los mismos sin comprometer las posibilidades de beneficiarse del tratamiento de la enfermedad de base.


Assuntos
COVID-19 , Hematologia , Argentina/epidemiologia , Teste para COVID-19 , Humanos , Pessoa de Meia-Idade , SARS-CoV-2
6.
Sci Rep ; 11(1): 16746, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408194

RESUMO

Several research efforts on cocoa have been focused on parameters for controlling the transformation process to guarantee homogeneity and quality of cocoa beans, the main raw material in the chocolate industry. The main changes that determine the final quality of cocoa-and also the product's homogeneity-occur during fermentation, given the great number of factors that affect the process. This research seeks to identify the most relevant factors affecting quality in order to offer higher-quality and more homogeneous cocoa for the chocolate industry. The dynamics of the fermentation process were observed in three contrasting locations, monitoring different variables and evaluating the final quality of the cocoa. Results show that temperature and pH profile are the key factors to be monitored and controlled in order to achieve high-quality cocoa beans.

7.
Medicina (B.Aires) ; 81(4): 536-545, ago. 2021. graf
Artigo em Inglês | LILACS | ID: biblio-1346504

RESUMO

Abstract Individuals with malignancies and COVID-19 have a lower survival compared with the general population. However, the information about the impact of COVID-19 on the whole hematological population is scarce. We aimed to describe the 30th day overall survival (OS) after COVID-19 infection in pa tients with a hematological disease in Argentina. A completely anonymous survey from the Argentine Society of Hematology was delivered to all the hematologists in Argentina; it started in April 2020. A cut-off to analyze the data was performed in December 2020 and, finally, 419 patients were reported and suitable for the analysis (average age: 58 years, 90% with malignant diseases). After the COVID-19 diagnosis, the 30-day OS for the whole population was 80.2%. From the entire group (419), 101 (24.1%) individuals required intensive care unit admission, where the 30-day OS was 46.6%. Among allogeneic stem cell transplant recipients, the 30-day OS was 70.3%. Factors associated with a low OS were two or more comorbidities, an active hematological disease and history of chemotherapy. In individuals with the three factors, the 30-day OS was 49.6% while the 30-day OS in those without those factors was 100%. Patients with hematological diseases have a higher mortality than the general population. This group represents a challenge and requires careful decision-making of the treatment in order not to compromise the chances of cure.


Resumen El presente estudio tuvo por objetivo primario conocer la mortalidad de pacientes con enfermedad hematológica que presentaron infección por COVID-19 en Argentina. Para ello se difundió una encuesta desde la Sociedad Argentina de Hematología (SAH) entre los hematológos para informar sobre los pacientes con enfermedades hematológicas y diagnóstico de infección por SARS- CoV-2, entre el 19/4/2020, y el 7/12/2020. Se incluyeron individuos de todas las edades con diagnóstico de enfermedad hematológica benigna o maligna e infección por SARS-CoV-2 confirmada por técnica de RT-PCR. Se analizaron 419 pacientes (mediana 58 años; 90% enfermedades malignas). La supervivencia al día 30 fue de 80.2%. La supervivencia fue menor en aquellos que requirieron internación (74.2%), cuidados intensivos (46.6%) y asistencia respiratoria mecánica (36.8%). Entre los trasplantados alogénicos la supervivencia fue 70.3%. Los factores vinculados a la supervivencia global fueron las comorbilidades, el estado de la enfermedad al momento de la infección y el antecedente de quimioterapia. Se pudo establecer un score en el que aquellos que tuvieron un puntaje de 4 alcanzaron una supervivencia del 49.6% al día 30, mientras que la de los pacientes con score 0 fue del 100% a 30 días. En comparación con la población general, los pacientes con enfermedades hematológicas presentan una mayor mortalidad vinculada al COVID-19, motivo por el cual es primordial definir pautas destinadas a disminuir la exposición de los mismos sin comprometer las posibilidades de beneficiarse del tratamiento de la enfermedad de base.


Assuntos
Humanos , Pessoa de Meia-Idade , COVID-19 , Hematologia , Argentina/epidemiologia , Teste para COVID-19 , SARS-CoV-2
8.
Neurochem Int ; 149: 105136, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34274381

RESUMO

Glioblastoma remains one of the most challenging and devastating cancers, with only a very small proportion of patients achieving 5-year survival. The current standard of care consists of surgery, followed by radiation therapy with concurrent and maintenance chemotherapy with the alkylating agent temozolomide. To date, this drug is the only one that provides a significant survival benefit, albeit modest, as patients end up acquiring resistance to this drug. As a result, tumor progression and recurrence inevitably occur, leading to death. Several factors have been proposed to explain this resistance, including an upregulated antioxidant system to keep the elevated intracellular ROS levels, a hallmark of cancer cells, under control. In this review, we discuss the mechanisms of chemoresistance -including the important role of glioblastoma stem cells-with emphasis on antioxidant defenses and how agents that impair redox balance (i.e.: sulfasalazine, erastin, CB-839, withaferin, resveratrol, curcumin, chloroquine, and hydroxychloroquine) might be advantageous in combined therapies against this type of cancer.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Antioxidantes/metabolismo , Neoplasias Encefálicas/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glioblastoma/metabolismo , Temozolomida/uso terapêutico , Animais , Antineoplásicos Alquilantes/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/fisiologia , Glioblastoma/tratamento farmacológico , Humanos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Temozolomida/farmacologia
9.
J Biomed Sci ; 28(1): 14, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33610185

RESUMO

BACKGROUND: Glutaminase isoenzymes GLS and GLS2 play apparently opposing roles in cancer: GLS acts as an oncoprotein, while GLS2 (GAB isoform) has context specific tumour suppressive activity. Some microRNAs (miRNAs) have been implicated in progression of tumours, including gliomas. The aim was to investigate the effect of GLS and GAB expression on both miRNAs and oxidative status in glioblastoma cells. METHODS: Microarray profiling of miRNA was performed in GLS-silenced LN229 and GAB-transfected T98G human glioblastoma cells and their wild-type counterparts. Results were validated by real-time quantitative RT-PCR. Oxidative status and antioxidant enzymes were determined by spectrophotometric or fluorescence assays in GLS-silenced LN229 and T98G, and GAB-transfected LN229 and T98G. RESULTS: MiRNA-146a-5p, miRNA-140-3p, miRNA-21-5p, miRNA-1260a, and miRNA-92a-3p were downregulated, and miRNA-1246 was upregulated when GLS was knocked down. MiRNA-140-3p, miRNA-1246, miRNA-1260a, miRNA-21-5p, and miRNA-146a-5p were upregulated when GAB was overexpressed. Oxidative status (lipid peroxidation, protein carbonylation, total antioxidant capacity, and glutathione levels), as well as antioxidant enzymes (catalase, superoxide dismutase, and glutathione reductase) of silenced GLS glioblastoma cells and overexpressed GAB glioblastoma cells significantly changed versus their respective control glioblastoma cells. MiRNA-1246, miRNA-1260a, miRNA-146a-5p, and miRNA-21-5p have been characterized as strong biomarkers of glioblastoma proliferation linked to both GLS silencing and GAB overexpression. Total glutathione is a reliable biomarker of glioblastoma oxidative status steadily associated to both GLS silencing and GAB overexpression. CONCLUSIONS: Glutaminase isoenzymes are related to the expression of some miRNAs and may contribute to either tumour progression or suppression through certain miRNA-mediated pathways, proving to be a key tool to switch cancer proliferation and redox status leading to a less malignant phenotype. Accordingly, GLS and GAB expression are especially involved in glutathione-dependent antioxidant defence.


Assuntos
Regulação Neoplásica da Expressão Gênica , Glioblastoma/metabolismo , Glutaminase/genética , MicroRNAs/metabolismo , Estresse Oxidativo , Linhagem Celular Tumoral , Regulação para Baixo , Glutaminase/metabolismo , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Regulação para Cima
11.
Neurol Clin Pract ; 11(6): e977-e979, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34993002
12.
Cell Biosci ; 10: 96, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817784

RESUMO

BACKGROUND: Openers of mitochondrial adenosine triphosphate-dependent potassium (mKATP) channels like diazoxide increase reactive oxygen species (ROS) production in cardiac cells and reduce Ca2+ elevations produced by ischemia-reperfusion, protecting the heart from damage. In this study we tested the hypothesis that opening mKATP channels regulates expression of the major components of store-operated Ca2+ entry (SOCE) STIM1 and Orai1. RESULTS: Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot experiments showed that diazoxide increased expression of STIM1 and Orai1 at the mRNA and protein levels, respectively, in adult rat cardiomyocytes. Immunofluorescence analyses revealed that diazoxide also disrupted the striated distribution pattern of STIM1. These effects were prevented by the ROS scavenger N-acetyl cysteine (NAC), the mKATP channel antagonist 5-hydroxydecanoate (5-HD), or the protein synthesis inhibitor cycloheximide (CHX). Confocal microscopy revealed that diazoxide also led to nuclear translocation of the transcription factors c-Fos and NFκB, which was also blocked by NAC or 5-HD. Finally, the MAPK pathway inhibitor UO126 attenuated diazoxide-induced upregulation of STIM1 and Orai1 expression. CONCLUSIONS: Our results suggest that opening mitochondrial potassium ATP channels with diazoxide upregulates the expression of STIM1 and Orai1 by de novo synthesis by a mechanism that involves NFkB, c-Fos, and ROS via MAPK/ERK signaling.

13.
Heliyon ; 6(2): e03416, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32140578

RESUMO

Cocoa production is a complex process where the conditions of the raw materials decisively impact the final quality of the product. Three universal clones (CCN51, ICS95, and TSH565) from the Department of Huila in Colombia were evaluated to characterize the ripening process of cocoa fruits. Maturity indicators were identified by following the evolution of basic fruit characteristics, including size, weight, seed count, depth and distance between grooves, width and length of the apex, diameter and length of the seed, moisture content, color parameters, fruit firmness, soluble solids content, pH, and acidity. The results indicated that each cocoa clone has a unique set of ripeness parameters: color for ICS95; firmness and weight of the seed for CCN51; and color, morphological characteristics of the apex and grooves, weight, moisture content, pH, and total soluble solids for TSH565. The establishment of reliable, practical, and objective ripeness indicators for each cocoa clone will allow more homogenous cocoa pods to be selected for fermentation, which will ultimately contribute to improved quality and homogeneity of cocoa and its derived products.

14.
J Pediatr Surg ; 55(10): 2042-2047, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32063367

RESUMO

PURPOSE: The aim was to evaluate if an abbreviated perioperative care bundle (APCB) is noninferior to the standard care, in terms of efficacy and safety, in pediatric patients undergoing bowel anastomoses. METHODS: A randomized, open, noninferiority trial with two parallel groups of equal size was carried out at the National Institute of Pediatrics in Mexico City, Mexico, from April 2016 to July 2018. The total number analyzed was 74 (37 per group). The APCB comprised same day admission, avoidance of mechanical bowel preparation, optimized antibiotic prophylaxis, and early feeding. Statistical analysis was done with Fisher's exact test or Chi2, and Student's T test. RESULTS: No significant differences were found for demographic variables and type of disease, either for the safety (anastomotic leakage, p 0.753; organ/space surgical site infection, p 0.500) or for some efficacy outcomes (ileus or bowel obstruction, p 0.693). Other efficacy outcomes were better in the study group, with shorter median times for feeding tolerance (19 h vs. 92 h, p < 0.001), for first bowel movement (15 h vs. 36 h, p < 0.001), and for discharge (1 vs. 6 days, p < 0.001). CONCLUSION: The abbreviated care bundle was proven to be as safe but more efficacious than the standard care. LEVEL OF EVIDENCE: I - randomized controlled trial with adequate statistical power.


Assuntos
Anastomose Cirúrgica , Procedimentos Cirúrgicos do Sistema Digestório , Pacotes de Assistência ao Paciente , Assistência Perioperatória , Anastomose Cirúrgica/métodos , Criança , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos Eletivos , Humanos , Pacotes de Assistência ao Paciente/efeitos adversos , Pacotes de Assistência ao Paciente/métodos , Assistência Perioperatória/efeitos adversos , Assistência Perioperatória/métodos , Complicações Pós-Operatórias
15.
Sci Rep ; 10(1): 2259, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-32042057

RESUMO

Glutaminase (GA) catalyzes the first step in mitochondrial glutaminolysis playing a key role in cancer metabolic reprogramming. Humans express two types of GA isoforms: GLS and GLS2. GLS isozymes have been consistently related to cell proliferation, but the role of GLS2 in cancer remains poorly understood. GLS2 is repressed in many tumor cells and a better understanding of its function in tumorigenesis may further the development of new therapeutic approaches. We analyzed GLS2 expression in HCC, GBM and neuroblastoma cells, as well as in monkey COS-7 cells. We studied GLS2 expression after induction of differentiation with phorbol ester (PMA) and transduction with the full-length cDNA of GLS2. In parallel, we investigated cell cycle progression and levels of p53, p21 and c-Myc proteins. Using the baculovirus system, human GLS2 protein was overexpressed, purified and analyzed for posttranslational modifications employing a proteomics LC-MS/MS platform. We have demonstrated a dual targeting of GLS2 in human cancer cells. Immunocytochemistry and subcellular fractionation gave consistent results demonstrating nuclear and mitochondrial locations, with the latter being predominant. Nuclear targeting was confirmed in cancer cells overexpressing c-Myc- and GFP-tagged GLS2 proteins. We assessed the subnuclear location finding a widespread distribution of GLS2 in the nucleoplasm without clear overlapping with specific nuclear substructures. GLS2 expression and nuclear accrual notably increased by treatment of SH-SY5Y cells with PMA and it correlated with cell cycle arrest at G2/M, upregulation of tumor suppressor p53 and p21 protein. A similar response was obtained by overexpression of GLS2 in T98G glioma cells, including downregulation of oncogene c-Myc. Furthermore, human GLS2 was identified as being hypusinated by MS analysis, a posttranslational modification which may be relevant for its nuclear targeting and/or function. Our studies provide evidence for a tumor suppressor role of GLS2 in certain types of cancer. The data imply that GLS2 can be regarded as a highly mobile and multilocalizing protein translocated to both mitochondria and nuclei. Upregulation of GLS2 in cancer cells induced an antiproliferative response with cell cycle arrest at the G2/M phase.


Assuntos
Carcinogênese/metabolismo , Pontos de Checagem do Ciclo Celular , Diferenciação Celular , Glutaminase/fisiologia , Neoplasias/metabolismo , Animais , Células COS , Linhagem Celular Tumoral , Proliferação de Células , Chlorocebus aethiops , Células Hep G2 , Humanos
16.
Front Mol Neurosci ; 12: 138, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191247

RESUMO

Signaling through bioactive lipids regulates nervous system development and functions. Lysophosphatidic acid (LPA), a membrane-derived lipid mediator particularly enriched in brain, is able to induce many responses in neurons and glial cells by affecting key processes like synaptic plasticity, neurogenesis, differentiation and proliferation. Early studies noted sustained elevations of neuronal intracellular calcium, a primary response to LPA exposure, suggesting functional modifications of NMDA and AMPA glutamate receptors. However, the crosstalk between LPA signaling and glutamatergic transmission has only recently been shown. For example, stimulation of presynaptic LPA receptors in hippocampal neurons regulates glutamate release from the presynaptic terminal, and excess of LPA induce seizures. Further evidence indicating a role of LPA in the modulation of neuronal transmission has been inferred from animal models with deficits on LPA receptors, mainly LPA1 which is the most prevalent receptor in human and mouse brain tissue. LPA1 null-mice exhibit cognitive and attention deficits characteristic of schizophrenia which are related with altered glutamatergic transmission and reduced neuropathic pain. Furthermore, silencing of LPA1 receptor in mice induced a severe down-regulation of the main glutaminase isoform (GLS) in cerebral cortex and hippocampus, along with a parallel sharp decrease on active matrix-metalloproteinase 9. The downregulation of both enzymes correlated with an altered morphology of glutamatergic pyramidal cells dendritic spines towards a less mature phenotype, indicating important implications of LPA in synaptic excitatory plasticity which may contribute to the cognitive and memory deficits shown by LPA1-deficient mice. In this review, we present an updated account of current evidence pointing to important implications of LPA in the modulation of synaptic excitatory transmission.

17.
Front Physiol ; 10: 1589, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32009985

RESUMO

Voltage-dependent Ca2+ channels and store-operated Ca2+ channels (SOCs) are the major routes of Ca2+ entry into mammalian cells. Previously, we reported that pharmacological preconditioning (PPC) leads to a decrease in the amplitude of L-type calcium channel current in the heart. In this study, we examined PPC-associated changes in SOC function. We measured adult cardiomyocyte membrane currents using the whole-cell patch-clamp technique, and we evaluated reactive oxygen species (ROS) production and intracellular Ca2+ levels in cardiomyocytes using fluorescent probes. Diazoxide (Dzx) and thapsigargin (Tg) were used to induce PPC and to deplete internal stores of Ca2+, respectively. Ca2+ store depletion generated inward currents with strong rectification, which were suppressed by the SOC blocker GSK-7975-A. These currents were completely abolished by PPC, an effect that could be countered with 5-hydroxydecanoate (5-HD; a selective mitochondrial ATP-sensitive K+ channel blocker), an intracellular mitochondrial energizing solution, or Ni2+ [a blocker of sodium-calcium exchanger (NCX)]. Buffering of ROS and intracellular Ca2+ also prevented PPC effects on SOC currents. Refilling of intracellular stores was largely suppressed by PPC, as determined by measuring intracellular Ca2+ with a fluorescent Ca2+ indicator. These results indicate that influx of Ca2+ through SOCs is inhibited by their ROS and Ca2+-dependent inactivation during PPC and that NCX is a likely source of PPC-inactivating Ca2+. We further showed that NCX associates with Orai1. Down-regulation of SOCs by PPC may play a role in cardioprotection following ischemia-reperfusion.

18.
Sci Signal ; 11(560)2018 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-30538175

RESUMO

The auxiliary ß4 subunit of the cardiac Cav1.2 channel plays a poorly understood role in gene transcription. Here, we characterized the regulatory effects of the ß4 subunit in H9c2 rat cardiac cells on the abundances of Ifnb mRNA [which encodes interferon-ß (IFN-ß)] and of the IFN-ß-related genes Ddx58, Ifitm3, Irf7, Stat2, Ifih1, and Mx1, as well as on the abundances of the antiviral proteins DDX58, IRF7, STAT2, and IFITM3. Knocking down the ß4 subunit in H9c2 cells reduced the expression of IFN-ß-stimulated genes. In response to inhibition of the kinase JAK1, the abundances of ß4 subunit mRNA and protein were decreased. ß4 subunit abundance was increased, and it translocated to the nucleus, in cells treated with IFN-ß, infected with dengue virus (DENV), or transfected with poly(I:C), a synthetic analog of double-stranded RNA. Cells that surrounded the virus-infected cells showed translocation of ß4 subunit proteins to nuclei in response to spreading infection. We showed that the ß4 subunit interacted with the transcriptional regulator IRF7 and that the activity of an Irf7 promoter-driven reporter was increased in cells overexpressing the ß4 subunit. Last, overexpressing ß4 in undifferentiated and differentiated H9c2 cells reduced DENV infection and decreased the abundance of the viral proteins NS1, NS3, and E-protein. DENV infection and poly(I:C) also increased the concentration of intracellular Ca2+ in these cells. These findings suggest that the ß4 subunit plays a role in promoting the expression of IFN-related genes, thereby reducing viral infection.


Assuntos
Canais de Cálcio/metabolismo , Interferon beta/imunologia , Miócitos Cardíacos/imunologia , Animais , Antivirais/farmacologia , Cálcio/metabolismo , Canais de Cálcio/genética , Células Cultivadas , Dengue/imunologia , Dengue/patologia , Dengue/prevenção & controle , Dengue/virologia , Vírus da Dengue/isolamento & purificação , Fator Regulador 7 de Interferon/genética , Fator Regulador 7 de Interferon/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/virologia , Regiões Promotoras Genéticas , Ratos , Transdução de Sinais , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo
19.
J Cardiovasc Pharmacol ; 72(5): 222-230, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30403388

RESUMO

INTRODUCTION AND METHODS: The effects of diazoxide on cardiac hypertrophy and miR-132 expression were characterized in adult rats and in cardiomyocytes. Diazoxide effects on reactive oxygen species (ROS) production and on the cAMP-response element binding (CREB) transcription factor's abundance in cardiomyocytes were also analyzed. ROS measurements used a fluorescent dye. Western blot analysis and quantitative Reverse Transcription Polymerase Chain Reaction were used to measure phosphorylated form of CREB (pCREB) abundance and miR-132 expression, respectively. RESULTS: Isoproterenol (ISO) induced cardiac hypertrophy, an effect that was mitigated by diazoxide. The rate of ROS production, CREB phosphorylation, and miR-132 expression increased after the addition of ISO. H2O2 increased pCREB abundance and miR-132 expression; upregulation of miR-132 was blocked by the specific inhibitor of CREB transcription, 666-15. Consistent with a role of ROS on miR-132 expression, diazoxide prevented the increase in ROS production, miR-132 expression, and pCREB abundance produced by ISO. Phosphorylation of CREB by ISO was prevented by U0126, an inhibitor of mitogen-activated protein kinase. CONCLUSIONS: Our data first demonstrate that diazoxide mitigates hypertrophy by preventing an increase in miR-132 expression. The mechanism likely involves less ROS production leading to less phosphorylation of CREB. Our data further show that ROS enhance miR-132 transcription, and that ISO effects are probably mediated by the mitogen-activated protein kinase pathway.


Assuntos
Cardiomegalia/prevenção & controle , Fármacos Cardiovasculares/farmacologia , Diazóxido/farmacologia , Isoproterenol , MicroRNAs/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Cardiomegalia/induzido quimicamente , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Células Cultivadas , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Modelos Animais de Doenças , Masculino , MicroRNAs/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
20.
Chemosphere ; 180: 239-246, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28411539

RESUMO

The degradation of methylene blue in aqueous solution as a model dye using a non thermal microwave (2.45 GHz) plasma jet at atmospheric pressure has been investigated. Argon has been used as feed gas and aqueous solutions with different concentrations of the dye were treated using the effluent from plasma jet in a remote exposure. The removal efficiency increased as the dye concentration decreased from 250 to 5 ppm. Methylene blue degrades after different treatment times, depending on the experimental plasma conditions. Thus, kinetic constants up to 0.177 min-1 were obtained. The higher the Ar flow, the faster the degradation rate. Optical emission spectroscopy (OES) was used to gather information about the species present in the gas phase, specifically excited argon atoms. Argon excited species and hydrogen peroxide play an important role in the degradation of the dye. In fact, the conversion of methylene blue was directly related to the density of argon excited species in the gas phase and the concentration of hydrogen peroxide in the aqueous liquid phase. Values of energy yield at 50% dye conversion of 0.296 g/kWh were achieved. Also, the use of two plasma applicators in parallel has been proven to improve energy efficiency.


Assuntos
Pressão Atmosférica , Azul de Metileno/química , Micro-Ondas , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Argônio/química , Peróxido de Hidrogênio/química , Cinética , Modelos Teóricos , Eliminação de Resíduos Líquidos/instrumentação , Águas Residuárias/química , Água/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos
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