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The sodium pump, or Na+/K+-ATPase (NKA), is an essential enzyme found in the plasma membrane of all animal cells. Its primary role is to transport sodium (Na+) and potassium (K+) ions across the cell membrane, using energy from ATP hydrolysis. This transport creates and maintains an electrochemical gradient, which is crucial for various cellular processes, including cell volume regulation, electrical excitability, and secondary active transport. Although the role of NKA as a pump was discovered and demonstrated several decades ago, it remains the subject of intense research. Current studies aim to delve deeper into several aspects of this molecular entity, such as describing its structure and mode of operation in atomic detail, understanding its molecular and functional diversity, and examining the consequences of its malfunction due to structural alterations. Additionally, researchers are investigating the effects of various substances that amplify or decrease its pumping activity. Beyond its role as a pump, growing evidence indicates that in various cell types, NKA also functions as a receptor for cardiac glycosides like ouabain. This receptor activity triggers the activation of various signaling pathways, producing significant morphological and physiological effects. In this report, we present the results of a comprehensive review of the most outstanding studies of the past five years. We highlight the progress made regarding this new concept of NKA and the various cardiac glycosides that influence it. Furthermore, we emphasize NKA's role in epithelial physiology, particularly its function as a receptor for cardiac glycosides that trigger intracellular signals regulating cell-cell contacts, proliferation, differentiation, and adhesion. We also analyze the role of NKA ß-subunits as cell adhesion molecules in glia and epithelial cells.
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ATPase Trocadora de Sódio-Potássio , ATPase Trocadora de Sódio-Potássio/metabolismo , ATPase Trocadora de Sódio-Potássio/química , Animais , Humanos , Membrana Celular/metabolismo , Transdução de Sinais , Ouabaína/farmacologia , Ouabaína/metabolismo , Glicosídeos Cardíacos/metabolismo , Glicosídeos Cardíacos/farmacologia , Sódio/metabolismoRESUMO
Introduction: The COVID-19 pandemic has accelerated universities' adaptation process toward online education, and it is necessary to know the students' attitudes toward this online education. Objective: To describe the evolution of the attitude toward online education among social science students at a public university in Peru in the academic year 2020, in the context of the COVID-19 pandemic. Methods: The study uses a quantitative approach, a descriptive level, a non-experimental design, and a longitudinal trend. The sample consisted of 1063 students at the beginning of the class period, 908 during the classes, and 1026 at the end of the class period. The questionnaire for data collection was the Attitude scale toward online education for university students during the COVID-19 pandemic. The data was collected using Google Forms. Results: As a result, the attitude towards online education was predominantly weak negative at the beginning (51.1 %) and during the classes (49.1 %), and weak positive (48.1 %) at the end of the class period. The changes were not significant when comparing the three moments, the levels of attitude toward, intention to adopt, ease of use, technical and pedagogical support, stressors, and need for online education (p-value <0.05). Conclusion: The evolution of the attitude towards online education in the sample had a non-significant positive trend. In the initial and process stages, a weak negative attitude prevailed due to the institution's inexperience and poor digital infrastructure; in the end, the attitude became weak and positive due to the adaptation and need for online education.
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Contrasting reports exist in the literature regarding the effect of chloroquine treatment on cellular zinc uptake or secretion. Here, we tested the effect of chloroquine administration in the Drosophila model organism. We show that larvae grown on a diet supplemented with 2.5 mg/ml chloroquine lose up to 50% of their stored zinc and around 10% of their total potassium content. This defect in chloroquine-treated animals correlates with the appearance of abnormal autophagolysosomes in the principal cells of the Malpighian tubules, where zinc storage granules reside. We further show that the reported increase of Fluozin-3 fluorescence following treatment of cells with 300 µM chloroquine for 1 h may not reflect increased zinc accumulation, since a similar treatment in Madin-Darby canine kidney cells results in a 36% decrease in their total zinc content. Thus, chloroquine should not be considered a zinc ionophore. Zinc supplementation plus chloroquine treatment restored zinc content both in vivo and in vitro, without correcting autophagic or other ionic alterations, notably in potassium, associated with the chloroquine treatment. We suggest that chloroquine or hydroxychloroquine administration to patients could reduce intracellular zinc storage pools and be part of the drug's mechanism of action.
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Drosophila melanogaster , Túbulos de Malpighi , Animais , Cloroquina/farmacologia , Cães , Hidroxicloroquina/farmacologia , Ionóforos/farmacologia , Potássio , Zinco/farmacologiaRESUMO
Abstract In recent months, rare cases of thrombosis at unusual sites associated with thrombocytopenia, occurring within a typical risk window (i.e., 4-28 days) after receiving SARS CoV2 vaccines, have been reported. Healthcare professionals should be prepared to detect these cases on time. The Expert Panel of the Knowledge Management and Transfer Network conducted a free search of the related literature. With the available information and the clinical expertise of the working group, we formulated, reviewed, and endorsed recommendations for the timely suspicion, diagnosis (case definitions, the use of initial laboratory and imaging tests, specific tests), and management of these thrombotic conditions. This document is considered a living document that will be updated as new evidence emerges, and recommendations may change over time.
Resumen En meses recientes se han reportado casos raros de trombocitopenia y trombosis en sitios inusuales, que ocurren dentro de una ventana de riesgo típica ( por ejemplo de 4 a 28 días) luego de recibir vacunas de SARS CoV 2. Los profesionales de la salud deben estar preparados para detectar estos casos a tiempo. Un panel de expertos y una red de transferencia de conocimiento realizó una búsqueda libre de literatura seleccionada. Con la información disponible y la experticia clínica del grupo de trabajo revisamos y dimos recomendaciones para la sospecha temprana, el diagnostico (definición de caso, el uso de pruebas de laboratorio especificas y de imágenes diagnósticas) para le manejo de estas condiciones tromboticas. Este documento es considerado un documento vivo que debe ser actualizado a medida que surja nueva evidencia y las recomendaciones vayan cambiando con el tiempo
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La investigación tuvo como objetivo determinar el impacto del aislamiento social por COVID-19 en los hábitos de consumo de los medios de comunicación de la población peruana. El estudio fue descriptivo simple y contó con una muestra de 3 618 personas de entre 18 y 69 años de edad, residentes en el Perú. Se aplicó en forma online un cuestionario tipo Likert de 36 ítems que midieron 6 dimensiones. La validez de contenido del instrumento fue evaluada por 20 expertos, y la validez de constructo y la confiabilidad fueron evaluadas en una muestra piloto de 200 sujetos. Los resultados evidenciaron un impacto positivo del aislamiento social en los hábitos de consumo de los medios de comunicación (54,4 por ciento), que fue más alto en la frecuencia de consumo de los medios de comunicación online (62,2 por ciento); la utilidad de los medios de comunicación (59,1 por ciento); la necesidad de información sobre la COVID-19 (47,7 por ciento); la interactividad a través de los medios de comunicación (43,7 por ciento) y la preferencia de los medios comunicación (41,9 por ciento); mientras que el impacto nulo fue preponderante en la frecuencia de consumo de los medios de comunicación offline (46 por ciento) y en la actitud hacia el tratamiento de la información sobre la COVID-19 (48,4 por ciento). Se concluyó que el impacto del aislamiento social por COVID-19 en los hábitos de consumo de los medios de comunicación en la población estudiada fue positivo, con mayor incidencia en los medios online(AU)
The research aimed to determine the impact of social isolation by COVID-19 on the media consumption habits among the Peruvian population. It was a simple descriptive study that included a sample of 3618 people between the ages of 18 and 69, residing in Peru. A Likert questionnaire of 36 items measuring 6 dimensions was applied online; the content validity of the instrument was evaluated by 20 experts, and the construct validity and reliability were evaluated in a pilot sample of 200 subjects. The results showed a positive impact of social isolation on media consumption habits (54,4 percent), which was higher in the frequency of online media consumption (62.2 percent), the usefulness of the media (59.1 percent), the need for information about COVID-19 (47.7 percent), the interactivity through the media (43.7 percent), and the media preference (41.9 percent); whereas the null impact was predominant in the frequency of offline media consumption (46 percent) and in the attitude towards the treatment of information about COVID-19 (48.4 percent). It was concluded that the impact of social isolation by COVID-19 on media consumption habits among the studied population was positive, with greater incidence in online media(AU)
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Humanos , Masculino , Feminino , Isolamento Social/psicologia , Meios de Comunicação , Indicadores de Impacto Social , COVID-19/epidemiologia , Peru , Epidemiologia Descritiva , Estudos TransversaisRESUMO
Programmed cell death (PCD) is an essential process for the immune system's development and homeostasis, enabling the remotion of infected or unnecessary cells. There are several PCD's types, depending on the molecular mechanisms, such as non-inflammatory or pro-inflammatory. Hemocytes are the main component of cellular immunity in bivalve mollusks. Numerous infectious microorganisms produce toxins that impair hemocytes functions, but there is little knowledge on the role of PCD in these cells. This study aims to evaluate in vitro whether marine toxins induce a particular type of PCD in hemocytes of the bivalve mollusk Crassostrea gigas during 4 h at 25°C. Hemocytes were incubated with two types of marine toxins: non-proteinaceous toxins from microalgae (saxitoxin, STX; gonyautoxins 2 and 3, GTX2/3; okadaic acid/dynophysistoxin-1, OA/DTX-1; brevetoxins 2 and 3, PbTx-2,-3; brevetoxin 2, PbTx-2), and proteinaceous extracts from bacteria (Vibrio parahaemolyticus, Vp; V. campbellii, Vc). Also, we used the apoptosis inducers, staurosporine (STP), and camptothecin (CPT). STP, CPT, STX, and GTX 2/3, provoked high hemocyte mortality characterized by apoptosis hallmarks such as phosphatidylserine translocation into the outer leaflet of the cell membrane, exacerbated chromatin condensation, DNA oligonucleosomal fragments, and variation in gene expression levels of apoptotic caspases 2, 3, 7, and 8. The mixture of PbTx-2,-3 also showed many apoptosis features; however, they did not show apoptotic DNA oligonucleosomal fragments. Likewise, PbTx-2, OA/DTX-1, and proteinaceous extracts from bacteria Vp, and Vc, induced a minor degree of cell death with high gene expression of the pro-inflammatory initiator caspase-1, which could indicate a process of pyroptosis-like PCD. Hemocytes could carry out both PCD types simultaneously. Therefore, marine toxins trigger PCD's signaling pathways in C. gigas hemocytes, depending on the toxin's nature, which appears to be highly conserved both structurally and functionally.
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Apoptose/efeitos dos fármacos , Toxinas Bacterianas/toxicidade , Crassostrea/efeitos dos fármacos , Hemócitos/efeitos dos fármacos , Toxinas Marinhas/toxicidade , Animais , Toxinas Bacterianas/isolamento & purificação , Caspases/metabolismo , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Crassostrea/imunologia , Crassostrea/metabolismo , Quebras de DNA de Cadeia Dupla , Hemócitos/imunologia , Hemócitos/metabolismo , Hemócitos/patologia , Fosfatidilserinas/metabolismo , Vibrio/metabolismo , Vibrio parahaemolyticus/metabolismoRESUMO
Objective: This study aimed to estimate asthma control at specialist treatment centers in four Latin American countries and assess factors influencing poor asthma control.Methods: Patients aged ≥12 years with an asthma diagnosis and asthma medication prescription, followed at outpatient specialist centers in Argentina, Chile, Colombia, and Mexico, were included. The study received all applicable ethical approvals. The Asthma Control Test (ACT) was used to classify patients as having controlled (ACT 20-25) or uncontrolled (ACT ≤19) asthma. Frequency and statistical tests were used to assess the association between hospital admissions/exacerbations/emergency department (ED) visits and uncontrolled asthma; multivariate logistic regression was used to assess the association of uncontrolled asthma with clinical/demographic variables.Results: A total of 594 patients were included. Overall controlled-asthma prevalence was 43.4% (95% confidence interval [CI]: 39.0, 47.4). Patients with uncontrolled asthma were more likely to be women (adjusted odds ratio [aOR]: 1.85; p = 0.003), non-white (aOR: 2.14; p < 0.001), obese (aOR: 1.71; p = 0.036), to have a low monthly family income (aOR: 1.75; p = 0.004), to have severe asthma (aOR:1.59; p = 0.26), and, compared with patients with controlled asthma, to have a higher likelihood of asthma exacerbations (34.5% vs. 15.9%; p < 0.001), hospital admissions (6.9% vs. 3.1%; p = 0.042), and ED visits (34.5% vs. 15.9%; p < 0.001) due to asthma.Conclusions: Even in specialist ambulatory services, fewer than half of patients were classified as having controlled asthma. The proportion of uncontrolled patients varied according to clinical and demographic variables.
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Asma/epidemiologia , Asma/fisiopatologia , Adolescente , Adulto , Fatores Etários , Idade de Início , Índice de Massa Corporal , Criança , Comorbidade , Estudos Transversais , Feminino , Recursos em Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , América Latina/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Razão de Chances , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Índice de Gravidade de Doença , Fatores Sexuais , Fatores Socioeconômicos , Adulto JovemRESUMO
BACKGROUND/AIMS: Ouabain, a well-known plant-derived toxin, is also a hormone found in mammals at nanomolar levels that binds to a site located in the a-subunit of Naâº,Kâº-ATPase. Our main goal was to understand the physiological roles of ouabain. Previously, we found that ouabain increases the degree of tight junction sealing, GAP junction-mediated communication and ciliogenesis. Considering our previous results, we investigated the effect of ouabain on adherens junctions. METHODS: We used immunofluorescence and immunoblot methods to measure the effect of 10 nM ouabain on the cellular and nuclear content of E-cadherin, ß-catenin and γ-catenin in cultured monolayers of Marin Darby canine renal cells (MDCK). We also studied the effect of ouabain on adherens junction biogenesis through sequential Ca²âº removal and replenishment. Then, we investigated whether c-Src and ERK1/2 kinases are involved in these responses. RESULTS: Ouabain enhanced the cellular content of the adherens junction proteins E-cadherin, ß-catenin and γ-catenin and displaced ß-catenin and γ-catenin from the plasma membrane into the nucleus. Ouabain also increased the expression levels of E-cadherin and ß-catenin in the plasma membrane after Ca²âº replenishment. These effects on adherens junctions were sensitive to PP2 and PD98059, suggesting that they depend on c-Src and ERK1/2 signaling. The translocation of ß-catenin and γ-catenin into the nucleus was specific because ouabain did not change the localization of the tight junction proteins ZO-1 and ZO-2. Moreover, in ouabain-resistant MDCK cells, which express a Naâº,Kâº-ATPase α1-subunit with low affinity for ouabain, this hormone was unable to regulate adherens junctions, indicating that the ouabain receptor that regulates adherens junctions is Naâº,Kâº-ATPase. CONCLUSION: Ouabain (10 nM) upregulated adherens junctions. This novel result supports the proposition that one of the physiological roles of this hormone is the modulation of cell contacts.
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Junções Aderentes/efeitos dos fármacos , Ouabaína/farmacologia , Junções Aderentes/metabolismo , Animais , Proteína Tirosina Quinase CSK , Caderinas/metabolismo , Cálcio/metabolismo , Núcleo Celular/metabolismo , Cães , Células Madin Darby de Rim Canino , Microscopia de Fluorescência , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismo , beta Catenina/metabolismo , gama Catenina/metabolismo , Quinases da Família src/metabolismoRESUMO
OBJECTIVE: This work aimed to determine if cataractous changes associated with EMT occurring in the K14E6 mice lenses are associated with TGF-ß and Wnt/ß-catenin signaling activation. MATERIALS AND METHODS: Cataracts of K14E6 mice were analysed histologically; and components of TGF-ß and Wnt/ß-catenin signaling were evaluated by Western blot, RT-qPCR, in situ RT-PCR, IHC, or IF technics. Metalloproteinases involved in EMT were also assayed using zymography. The endogenous stabilisation of Smad7 protein was also assessed using an HDAC inhibitor. RESULTS: The K14E6 mice, which displayed binocular cataracts in 100% of the animals, exhibited loss of tissue organisation, cortical liquefaction, and an increase in the number of hyperproliferative-nucleated cells with mesenchymal-like characteristics in the lenses. Changes in lenses' cell morphology were due to actin filaments reorganisation, activation of TGF-ß and Wnt/ß-catenin pathways, and the accumulation of MTA1 protein. Finally, the stabilisation of Smad7 protein diminishes cell proliferation, as well as MTA1 protein levels. CONCLUSION: The HPV16-E6 oncoprotein induces EMT in transgenic mice cataracts. The molecular mechanism may involve TGF-ß and Wnt/ß-catenin pathways, suggesting that the K14E6 transgenic mouse could be a useful model for the study or treatment of EMT-induced cataracts.
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Catarata/metabolismo , Transição Epitelial-Mesenquimal , Papillomavirus Humano 16/metabolismo , Proteínas Oncogênicas Virais/biossíntese , Proteínas Repressoras/biossíntese , Fator de Crescimento Transformador beta/metabolismo , Via de Sinalização Wnt , Animais , Catarata/genética , Catarata/patologia , Modelos Animais de Doenças , Papillomavirus Humano 16/genética , Camundongos , Camundongos Transgênicos , Proteínas Oncogênicas Virais/genética , Proteínas Repressoras/genética , Fator de Crescimento Transformador beta/genéticaRESUMO
Histamine H3 receptors (H3Rs) signal through Gαi/o proteins and are found in neuronal cells as auto- and hetero-receptors. Alternative splicing of the human H3R (hH3R) originates 20 isoforms, and the mRNAs of two receptors of 445 and 365 amino acids (hH3R445 and hH3R365) are widely expressed in the human brain. We previously showed that the hH3R445 stably expressed in CHO-K1 cells experiences homologous desensitization. The hH3R365 lacks 80 residues in the third intracellular loop, and in this work we therefore studied whether this isoform also experiences homologous desensitization and the possible differences with the hH3R445. In clones of CHO-K1 cells stably expressing similar receptor levels (211 ± 12 and 199 ± 16 fmol/mg protein for hH3R445 and hH3R365, respectively), there were no differences in receptor affinity for selective H3R ligands or for agonist-induced [35S]-GTPγS binding to membranes and inhibition of forskolin-stimulated cAMP accumulation in intact cells. For both cell clones, pre-incubation with the H3R agonist RAMH (1 µM) resulted in functional receptor desensitization, as indicated by cAMP accumulation assays, and loss of receptors from the cell surface and reduced affinity for the agonist immepip in cell membranes, evaluated by radioligand binding. However, functional desensitization differed in the maximal extent (96 ± 15% and 58 ± 8% for hH3R445 and hH3R365, respectively) and the length of pre-exposure required to reach the maximum desensitization (60 and 30 min, respectively). Furthermore, the isoforms differed in their recovery from desensitization. These results indicate that the hH3R365 experiences homologous desensitization, but that the process differs between the isoforms in time-course, magnitude and re-sensitization.