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The article presents the results of qualitative action research on armed violence with health and education professionals and territorial community services in Manguinhos, Rio de Janeiro, Brazil. It is justified by the urgent nature of this violence in the territory and aims to identify its impacts on their health and work, coping, protection, and care strategies. The effects of armed violence on health and education professionals and the territory are discussed through interviews and focus groups with participant observation, identifying some of its transversalities, such as the Brazilian State racist public security policy based on a warlike logic of confrontation with groups with armed control of the territory, which makes life precarious by exposing residents and workers to constant risks, weakening the community fabric and preventing full access to health and education.
O artigo apresenta resultados de uma pesquisa qualitativa sobre violência armada, do tipo pesquisa-ação, com profissionais de saúde e de educação e serviços comunitários territoriais em Manguinhos/RJ. Justifica-se pela premência dessa violência no território, tendo como objetivo identificar seus impactos na saúde e no trabalho, assim como as estratégias de enfrentamento, proteção e cuidado empreendidas. A partir de entrevistas e grupos focais com profissionais de saúde e da educação e observação participante, discutem-se os efeitos da violência armada sobre elas(es) e o território, identificando algumas de suas transversalidades, como a política de segurança pública racista empreendida pelo Estado brasileiro, baseada numa lógica bélica de confronto com grupos que têm domínio armado de território, que precariza a vida ao expor moradoras(es) e trabalhadoras(es) a riscos constantes, enfraquece o tecido comunitário e impede o pleno acesso à saúde e à educação.
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Grupos Focales , Personal de Salud , Violencia , Brasil , Humanos , Masculino , Femenino , Adaptación Psicológica , Entrevistas como Asunto , AdultoRESUMEN
The present study modeled the adsorption process of the drug diclofenac sodium on activated charcoal. For this purpose, a mass balance-based model was used considering a fixed bed column. The mass transfer rate in the solid phase was represented by a driving force model proposed in this study, and a gamma exponent with a range of 0 > γ ≤ 2 was assigned to the model. Different isotherms were adopted to represent the equilibrium at the solid/liquid interface: the Langmuir, Freundlich, Sips and Redlich-Peterson isotherms. The modeling was approached from the perspective of Bayesian statistics, and the Markov chain Monte Carlo method was used for parameter estimation. Model validation was performed with experimental data obtained under different operating conditions of initial concentration ($C_{0.
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Teorema de Bayes , Carbón Orgánico , Diclofenaco , Diclofenaco/química , Adsorción , Carbón Orgánico/química , Método de Montecarlo , Modelos QuímicosRESUMEN
INTRODUCTION AND OBJECTIVES: Cardiovascular diseases (CVD) and cancer are some of the most recognized causes of mortality and morbidity worldwide. Cancer is the second leading cause of death in heart failure (HF) populations. Recent studies have hypothesized that HF might promote the development and progression of cancer. We aim to analyze and discuss the most recent evidence on the relationship between HF and cancer development. METHODS: From inception to November 2022, we searched PubMed, Web of Science and ClinicalTrials.gov for relevant articles on patients with HF and a subsequent cancer diagnosis that reported outcomes of overall and site-specific cancer incidence, or mortality. RESULTS: Of 2401 articles identified in our original search, 13 articles met our criteria. Studies reporting risk rate estimates were summarized qualitatively. Studies reporting hazard ratios (HRs), or relative risks were combined in a meta-analysis and revealed that HF was associated with an increased overall cancer incidence with a HR=1.30 (95% CI: 1.04-1.62) compared with individuals without HF. Subgroup analyses by cancer type revealed increased risk for lung cancer (HR=1.87; 95% CI: 1.28-2.73), gastrointestinal cancer (HR=1.22; 95% CI: 1.03-1.45), hematologic cancer (HR=1.60; 95% CI: 1.23-2.08) and female reproductive cancer (HR=1.67; 95% CI: 1.27-2.21). Mortality from cancer was higher in HF patients compared with non-HF subjects with a HR=2.17 (95% CI: 1.23-3.84). CONCLUSIONS: Our systematic review and meta-analysis revealed that HF may result in a subsequent increase in cancer incidence as well as in cancer-related mortality. The most common cancer subtypes in HF patients were lung, female reproductive system, and hematologic cancers. Further research is needed to understand this association better and to provide the best cardiological and oncological care.
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Insuficiencia Cardíaca , Neoplasias , Humanos , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/complicaciones , Neoplasias/complicaciones , Neoplasias/epidemiología , IncidenciaRESUMEN
BACKGROUND AND OBJECTIVE: Individuals after stroke are likely to deal with the possible development of sarcopenia and reduced physical activity levels. The purpose of this study was to compare sarcopenia of individuals with chronic stroke who were stratified according to their physical activity levels, and to evaluate the relationship between sarcopenia and physical activity levels. MATERIALS AND METHODS: This cross-sectional study was conducted with individuals after chronic stroke recruited from the general community. Individuals were submitted to sarcopenia screening (SARC-F questionnaire) and assessment of physical activity levels (Human Activity Profile questionnaire) to classify the individuals as impaired, moderately active, and active according to their Adjusted Activity Status (AAS). ANOVA was used to investigate the sarcopenia between groups and Pearson's coefficient to investigate the association among variables. RESULTS: Fifty-four individuals with a mean age of 56 ± 17.4 years were included. Twenty-one percent of the individuals were screened for sarcopenia. Inactive individuals had higher mean scores in the SARC-F (3.6 ± 2.1 points), whereas moderately active and active individuals presented lower mean scores in the same questionnaire, being 1.2 ± 1.1 points and 0.5 ± 0.7 points, respectively. A statistically significant inverse and high association was found between sarcopenia and physical activity levels (r = -0.716; p < 0.01). CONCLUSION: Sarcopenia was found to be higher in individuals after chronic stroke with lower physical activity levels considered inactive when compared to individuals with higher physical activity levels. Furthermore, there was an inverse relationship between sarcopenia and physical activity level in stroke survivors.
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Sarcopenia , Humanos , Adulto , Persona de Mediana Edad , Anciano , Sarcopenia/diagnóstico , Sarcopenia/epidemiología , Estudios Transversales , Encuestas y Cuestionarios , Ejercicio Físico , Evaluación GeriátricaRESUMEN
In 2020, breast cancer (BC) has surpassed lung cancer as the most diagnosed cancer in the world. Tumor microenvironment (TME) plays a critical role in resistance to standard therapies and tumor progression. Two key factors within the TME include adenosine, an immunosuppressive molecule, and glucose, which serves as the primary energy source for tumor cells. In this scenario, inhibiting the purinergic pathway and glucose uptake might be a promising strategy. Therefore, we sought to evaluated different treatment approaches in BC cells (Dapagliflozin, a SGLT2 inhibitor; Paclitaxel, the standard chemotherapy for BC; and ARL67156/APCP, inhibitors of CD39 and CD73, respectively). The expression of some membrane markers relevant to resistance was assessed. BC cell-lines (MCF-7 and MDA-MB-231) were co-treated and cell viability, cell cycle, and annexin/PI assays were performed. Our analysis showed promising results, where the combination of these compounds led to cell death by apoptosis/necrosis and cell cycle arrest. Dapagliflozin showed more impact on early apoptosis, whereas Paclitaxel led to late apoptosis/necrosis as the main mechanism of cell death. Inhibiting purinergic signaling also contributed to reducing cell viability together with the other drugs, suggesting it could have an influence on breast cancer survival mechanisms. Indeed, the overexpression of the NT5E gene in patients with ER+ tumors is strongly associated with reduced overall survival and progression-free interval. However, more studies are needed to fully understand the interactions and mechanism underlying these co-treatment multi-targeting approaches.
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Compuestos de Bencidrilo , Neoplasias de la Mama , Glucósidos , Humanos , Femenino , Neoplasias de la Mama/patología , Línea Celular Tumoral , Paclitaxel/farmacología , Apoptosis , Necrosis , Proliferación Celular , Microambiente TumoralRESUMEN
Malignant gliomas are highly heterogeneous glia-derived tumors that present an aggressive and invasive nature, with a dismal prognosis. The multi-dimensional interactions between glioma cells and other tumor microenvironment (TME) non-tumoral components constitute a challenge to finding successful treatment strategies. Several molecules, such as extracellular purines, participate in signaling events and support the immunosuppressive TME of glioma patients. The purinergic signaling and the ectoenzymes network involved in the metabolism of these extracellular nucleotides are still unexplored in the glioma TME, especially in lower-grade gliomas (LGG). Also, differences between IDH-mutant (IDH-Mut) versus wild-type (IDH-WT) gliomas are still unknown in this context. For the first time, to our knowledge, this study characterizes the TME of LGG, high-grade gliomas (HGG) IDH-Mut, and HGG IDH-WT patients regarding purinergic ectoenzymes and P1 receptors, focusing on tumor-infiltrating lymphocytes. Here, we show that ectoenzymes from both canonical and non-canonical pathways are increased in the TME when compared to the peripheral blood. We hypothesize this enhancement supports extracellular adenosine generation, hence increasing TME immunosuppression.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/patología , Linfocitos Infiltrantes de Tumor/patología , Isocitrato Deshidrogenasa/genética , Glioma/patología , Pronóstico , Mutación , Microambiente TumoralRESUMEN
Resumo O artigo apresenta resultados de uma pesquisa qualitativa sobre violência armada, do tipo pesquisa-ação, com profissionais de saúde e de educação e serviços comunitários territoriais em Manguinhos/RJ. Justifica-se pela premência dessa violência no território, tendo como objetivo identificar seus impactos na saúde e no trabalho, assim como as estratégias de enfrentamento, proteção e cuidado empreendidas. A partir de entrevistas e grupos focais com profissionais de saúde e da educação e observação participante, discutem-se os efeitos da violência armada sobre elas(es) e o território, identificando algumas de suas transversalidades, como a política de segurança pública racista empreendida pelo Estado brasileiro, baseada numa lógica bélica de confronto com grupos que têm domínio armado de território, que precariza a vida ao expor moradoras(es) e trabalhadoras(es) a riscos constantes, enfraquece o tecido comunitário e impede o pleno acesso à saúde e à educação.
Abstract The article presents the results of qualitative action research on armed violence with health and education professionals and territorial community services in Manguinhos, Rio de Janeiro, Brazil. It is justified by the urgent nature of this violence in the territory and aims to identify its impacts on their health and work, coping, protection, and care strategies. The effects of armed violence on health and education professionals and the territory are discussed through interviews and focus groups with participant observation, identifying some of its transversalities, such as the Brazilian State racist public security policy based on a warlike logic of confrontation with groups with armed control of the territory, which makes life precarious by exposing residents and workers to constant risks, weakening the community fabric and preventing full access to health and education.
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A cartilha é um material educativo fruto da pesquisa "Migração, saúde e violências: experiências de trabalhadoras(es) migrantes e refugiadas(os) no Rio de Janeiro", durante a qual foram escutadas(os) migrantes e refugiadas(os) residentes no Brasil, especificamente no estado do Rio de Janeiro. Os deslocamentos humanos são uma realidade de dimensões globais e garantir o acesso e a permanência de migrantes e refugiadas(os) em postos de trabalho seguros, saudáveis e não violentos deve ser uma das finalidades de sociedades que prezam pela justiça social. A migração e o refúgio podem trazer mudanças na forma de organização familiar e a necessidade de buscar emprego, casa, estudo, relações de amizade e redes de apoio. Ao mesmo tempo em que a migração e o refúgio podem ser experiências que tragam novos recomeços, os sentimentos de incerteza, insegurança, medo, saudades e preocupação estão presentes no cotidiano de migrantes e refugiadas(os) e se expressam também na esfera do trabalho. Associado a isso, o mundo do trabalho tem passado por profundas transformações, principalmente nas últimas cinco décadas, que vêm impactando a vida de trabalhadoras(es), como o aumento do desemprego, contratações temporárias, baixos salários e a permanência de trabalho escravizado e forçado. Portanto, é preciso reconhecê-las para enfrentá-las, de modo a garantir um ambiente de trabalho seguro e saudável para todas(os). (AU)
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Atención Primaria de Salud , Refugiados , Legislación Laboral , Salud Pública , Grupos de Población , Equidad de Género , Vulnerabilidad SocialRESUMEN
Background: Due to social restrictions caused by the pandemic, there was a need to validate outcome measures that could be administered by telephone call. Administration by telephone allows to remotely follow up stroke survivors since most of them have mobility restrictions. This study aims to investigate the validity of the Duke Activity Status Index (DASI) questionnaire administration to chronic stroke survivors through telephone call. Methods: This is a cross-sectional study, developed according to COSMIN and GRRAS recommendations. It was recruited chronic stroke survivors, who answered the DASI questionnaire in two different time-points, in person and after a period of 5-7 days through a telephone call. Results: Out of 260 subjects, 50 individuals (52% women) with a mean age of 56 ± 17 years were included. No statistically significant differences were observed (MD = -0.88; SD:4.14; 95% CI, -2.06 to 0.28; p = 0.13) on the total score of DASI administered in person and by telephone call. There was a very high agreement between the administration modes (ICC - 0.99; 95% CI, 0.94-0.98; p < 0.05). The Kappa coefficient ranged from 0.390 to 1.000, with the first item showing the best agreement (k = 1.000) and the fourth showing the worst agreement (k = 0.390). Conclusions: The DASI questionnaire is valid to assess functional capacity and can be administered through telephone in chronic stroke survivors. Thus, clinicians and researchers may decide to avoid patient transportations administering DASI through telephone call, as a reliable measure for stroke survivors.
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Objetivo: relatar o uso do diamino fluoreto de prata (DFP) para tratamento da cárie na primeira infância em paciente não colaboradora de 3 anos. Relato do caso: ao exame clínico inicial, realizado com auxílio da estabilização protetora, notou-se que a paciente estava na fase de dentição decídua, possuía excessivo acúmulo de biofilme visível, sem sensibilidade ou qualquer outro sintoma, porém apresentando múltiplas lesões de cárie ativas em todos os dentes, exceto nos incisivos inferiores. Optou-se pelo uso do DFP 30% (Cariestop®) para o tratamento das lesões de cárie e também como alternativa para o manejo do comportamento, que foi classificado usando a Escala Comportamental de Frankl. Já na consulta inicial foi realizada a primeira aplicação, durante 2 minutos, diretamente sobre as lesões cavitadas em dentina dos dentes do hemiarco superior esquerdo, após profilaxia dentária prévia. Na segunda consulta, foi realizada a aplicação do produto nas lesões do hemiarco superior direito, enquanto no terceiro atendimento foi aplicado o DFP nos molares e caninos inferiores. Em todas as consultas foi realizada instrução de higiene bucal e de dieta com a responsável. Resultados: no decorrer do tratamento a paciente apresentou expressiva melhora no comportamento, que havia sido definitivamente negativo na primeira consulta. Ela sentou-se sozinha na cadeira e não precisou da estabilização protetora na última consulta, apresentando comportamento positivo. Verificou-se também a paralisação das lesões de cárie em decorrência do uso do DFP. Conclusão: o uso de DFP para tratamento de lesões cavitadas de cárie em pacientes não colaboradores foi considerado uma estratégia eficaz tanto para paralisação das lesões quanto para auxílio no condicionamento do comportamento.
Objective: to report the use of silver diamine fluoride (SDF) for the treatment of caries in early childhood in a 3-year-old non-collaborating patient. Case report: at the initial clinical examination, performed with protective stabilization, it was verified that the patient was in the primary dentition period, had excessive accumulation of visible biofilm, no dental sensibility or any other symptom, but had multiple active caries lesions in all teeth except the lower incisors. It was decided to use SDF 30% (Cariestop®) for the treatment of caries lesions and also as an alternative for managing behavior, which was classified using the Frankl Behavioral Scale. In the initial consultation, the first application was performed, for 2 minutes, directly on the dentin cavitated lesions of the teeth of the upper left hemiarch, after previous dental prophylaxis. In the second appointment, the product was applied into the lesions on the upper right hemiarch, while in the third visit, the SDF was applied to the lower molars and canines. In all consultations, instructions on oral hygiene and diet were given to the guardian. Results: during the treatment, the patient showed a significant improvement in behavior, which had been definitely negative in the first consultation. She sat alone in the dental chair and did not need protective stabilization at her last visit, showing positive behavior. There was also an arrest of carious lesions due to the use of DFP. Conclusion: The use of SDF for the treatment of cavitated carious lesions in non- collaborating patients was considered an effective strategy both for arresting the lesions and for improving the condition behavior.
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Femenino , Preescolar , Caries Dental , Cariostáticos , Control de la ConductaRESUMEN
Staphylococcus spp. and Mammaliicoccus spp. colonize the skin and mucosa of humans and other animals and are responsible for several opportunistic infections. Staphylococci antibiotic resistance may be present in the environment due to the spread of treated and untreated manure from the livestock industry due to antibiotic use to disease control or growth promoter. In this work, we analyzed the species distribution and antimicrobial susceptibility of Staphylococcus and Mammaliicoccus species along different sites of a swine manure treatment plant from Southeastern Brazil. Bacterial colonies were obtained on mannitol salt agar, selected after catalase test and Gram staining, and finally identified by mass spectrometry and sequencing of the tuf gene. According to the results, S.cohnii and S. simulans were the most prevalent species. Antibiotic resistance test revealed that several strains were resistant to multiple drugs, with high levels of chloramphenicol resistance (98%), followed by erythromycin (79%), tetracycline (73%), gentamicin (46%), ciprofloxacin (42%), cefoxitin (18%), sulfamethoxazole + trimethoprim (12%), and linezolid (4%). In addition, gene detection by PCR showed that all strains carried at least 2 resistance genes and one of them carried all 11 genes investigated. Using the GTG5-PCR approach, a high genetic similarity was observed between some strains that were isolated from different points of the treatment plant. Although some were seemingly identical, differences in their resistance phenotype and genotype suggest horizontal gene transfer. The presence of resistant bacteria and resistance genes along the treatment system highlights the potential risk of contamination by people in direct contact with these animals and the soil since the effluent is used as a biofertilizer in the surrounding environment.
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Antibacterianos , Staphylococcus , Humanos , Porcinos , Animales , Antibacterianos/farmacología , Estiércol , Farmacorresistencia Bacteriana/genética , Cefoxitina , Pruebas de Sensibilidad MicrobianaRESUMEN
PURPOSE: Although risk-stratified chemotherapy regimens improve B-cell acute lymphoblastic leukemia (B-ALL) clinical outcome, relapse occurs in a significant number of cases. The identification of new therapeutic targets as well as prognostic and diagnostic biomarkers can improve B-ALL patients' clinical outcomes. Purinergic signaling is an important pathway in cancer progression, however the expression of ectonucleotidases and their impact on immune cells in B-ALL lacks exploration. We aimed to analyze the expression of ectonucleotidases in B-ALL patients' lymphocyte subpopulations. METHODS: Peripheral blood samples from 15 patients diagnosed with B-ALL were analyzed. Flow cytometry was used to analyze cellularity, expression level of CD38, CD39, and CD73, and frequency of [Formula: see text], and [Formula: see text] in lymphocyte subpopulations. Plasma was used for cytokines (by CBA kit) and adenine nucleosides/nucleotides detection (by HPLC). RESULTS: Comparing B-ALL patients to health donors, we observed an increase of CD4 + and CD8 + T-cells. In addition, a decrease in CD38 expression in B and Treg subpopulations and an increase in CD39+ CD73+ frequency in Breg and CD8+ T-cells. Analyzing cytokines and adenine nucleosides/nucleotides, we found a decrease in TNF, IL-1ß, and ADO concentrations, together with an increase in AMP in B-ALL patients' plasma. CONCLUSION: As immunomodulators, the expression of ectonucleotidases might be associated with activation states, as well as the abundance of different cellular subsets. We observed a pro-tumor immunity expression profile in B-ALL patients at diagnosis, being associated with cell exhaustion and immune evasion in B-ALL.
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Este estudo teve como objetivo propor um modelo explicativo de não adesão ao paradigma psicossocial da saúde mental a partir dos estereótipos, das crenças sobre a etiologia da doença mental, da percepção de ameaça e do preconceito. Para tanto, contou-se com a participação de 400 universitários, com média de idade de 24,64 anos (DP = 6, 64), sendo a maioria do sexo feminino (75,6%). Para a proposição do modelo, foi realizada uma path analysis. O modelo proposto demonstrou que quanto maior a percepção de ameaça e a concordância com o estereótipo de incapacidade, menor o apoio ao paradigma psicossocial. Ademais, verificou-se que as crenças acerca da etiologia da doença mental e os estereótipos estão na base da percepção de ameaça e todas essas variáveis juntas predizem maior preconceito. Os achados desta pesquisa fornecem subsídios científicos para a realização de intervenções eficazes e consistentes que fortaleçam o paradigma psicossocial no cenário nacional. (AU)
This study aimed to propose an explanatory model of non-adherence to the psychosocial paradigm of mental health based on stereotypes, beliefs about the etiology of mental illness, perception of threat, and prejudice. Participants included a total of 400 university students, with a mean age of 24.64 years (SD = 6, 64), mostly women (75.6%). A path analysis was performed to propose the model, which showed that the greater the perception of threat and the agreement with the disability stereotype, the lower the support for the psychosocial paradigm. Furthermore, it was found that beliefs about the etiology of mental illness and stereotypes are at the basis of the perception of threat and all these variables together predict greater prejudice. The findings of this research provide scientific support for effective and consistent interventions that strengthen the psychosocial paradigm on the national scene. (AU)
Este estudio tuvo como objetivo proponer un modelo explicativo de la no adherencia al paradigma psicosocial de la salud mental basado en estereotipos, creencias sobre la etiología de la enfermedad mental, percepción de amenaza y prejuicio. Para ello participaron 400 estudiantes universitarios, con una edad media de 24,64 años (DS = 6,64), siendo la mayoría mujeres (75,6 %). Para la proposición del modelo, se realizó un path análisis. El modelo sugerido demostró que, a mayor percepción de amenaza y concordancia con el estereotipo de discapacidad, menor apoyo al paradigma psicosocial. Además, se encontró que las creencias sobre la etiología de la enfermedad mental y los estereotipos están en la base de la percepción de amenaza y todas estas variables en conjunto predicen un mayor prejuicio. Los hallazgos de esta investigación brindan soporte científico para ejecutar intervenciones efectivas y consistentes que fortalezcan el paradigma psicosocial en el escenario nacional. (AU)
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Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Prejuicio , Estereotipo , Salud Mental , Funcionamiento Psicosocial , Estudiantes , Estudiantes de Medicina , Estudiantes de Enfermería , Universidades , Análisis Multivariante , Análisis de Regresión , Reproducibilidad de los Resultados , Reforma de la Atención de Salud , Exactitud de los Datos , Correlación de Datos , Distrés Psicológico , Factores SociodemográficosRESUMEN
Oral traumatic ulcers (OTU) are common in dental routine, and the control of proinflammatory cytokines, such as the tumor necrosis factor-alpha (TNF-α), may interfere with OTU repair. Our aim was to evaluate the role of TNF-α in the healing process of OTU in rats. Wistar male rats were divided into six groups: a control-group (treated with 0.1 mL/kg of saline) and five groups treated with anti-TNF-α infliximab (INF) at 1, 3, 5, 7, and 10 mg/kg immediately before OTU production. The animals were weighed (day 0) and euthanized on days 1, 3, 7, 14 and 21 after ulceration. The ulcers were clinically measured, and the mucosa samples were histologically (scores 0-4), histochemically (collagen assay (pircrosirius)), histomorphometrically (cell counting), and immunohistochemically (TNF-α, α-smooth-muscle-actin (α-SMA), monocyte-chemoattractive-protein-1 (MCP-1), interleukin-8 (IL-8), and fibroblast-growth-factor (FGF)) analyzed. The Evans blue assay was used to measure the vascular permeability. ANOVA-1-2-way/Bonferroni, Kruskal-Wallis/Dunn, and correlation analyses were performed (GraphPad Prism 5.0, p < 0.05). High doses of INF reduced the OTU area (p = 0.043), body mass loss (p = 0.023), vascular permeability (p < 0.001), and reduced delayed histologic scores (p < 0.05), polymorphonuclear (p < 0.001) and mononuclear (p < 0.001) cells, blood vessel counting (p = 0.006), and total (p < 0.001), type-I (p = 0.018), and type-III (p < 0.001) collagen. INF treatment reduced TNF-α immunostaining and delayed MPC-1, FGF, and α-SMA expression, with little/none influence in IL-8 immunostaining. TNF-α blockage by INF reduced acute inflammation in OTU but delayed cell migration and wound healing.
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Úlceras Bucales , Factor de Necrosis Tumoral alfa , Actinas , Animales , Colágeno , Citocinas , Azul de Evans/uso terapéutico , Inflamación/tratamiento farmacológico , Infliximab/farmacología , Infliximab/uso terapéutico , Interleucina-8/uso terapéutico , Masculino , Úlceras Bucales/tratamiento farmacológico , Úlceras Bucales/patología , Ratas , Ratas Wistar , Inhibidores del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfa/metabolismo , Úlcera , Cicatrización de HeridasRESUMEN
Caveolin-1 (Cav-1) is an integral membrane protein present in all organelles, responsible for regulating and integrating multiple signals as a platform. Mitochondria are extremely adaptable to external cues in chronic liver diseases, and expression of Cav-1 may affect mitochondrial flexibility in hepatic stellate cells (HSCs) activation. We previously demonstrated that exogenous expression of Cav-1 was sufficient to increase some classical markers of activation in HSCs. Here, we aimed to evaluate the influence of exogenous expression and knockdown of Cav-1 on regulating the mitochondrial plasticity, metabolism, endoplasmic reticulum (ER)-mitochondria distance, and lysosomal activity in HSCs. To characterize the mitochondrial, lysosomal morphology, and ER-mitochondria distance, we perform transmission electron microscope analysis. We accessed mitochondria and lysosomal networks and functions through a confocal microscope and flow cytometry. The expression of mitochondrial machinery fusion/fission genes was examined by real-time polymerase chain reaction. Total and mitochondrial cholesterol content was measured using Amplex Red. To define energy metabolism, we used the Oroboros system in the cells. We report that GRX cells with exogenous expression or knockdown of Cav-1 changed mitochondrial morphometric parameters, OXPHOS metabolism, ER-mitochondria distance, lysosomal activity, and may change the activation state of HSC. This study highlights that Cav-1 may modulate mitochondrial function and structural reorganization in HSC activation, being a potential candidate marker for chronic liver diseases and a molecular target for therapeutic intervention.
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Caveolina 1 , Células Estrelladas Hepáticas , Caveolina 1/genética , Caveolina 1/metabolismo , Colesterol/metabolismo , Células Estrelladas Hepáticas/metabolismo , Humanos , Cirrosis Hepática/patología , Proteínas de la Membrana/metabolismo , Mitocondrias/metabolismoRESUMEN
Error-related electroencephalographic (EEG) signals have been widely studied concerning the human cognitive capability of differentiating between erroneous and correct actions. Midfrontal error-related negativity (ERN) and theta band oscillations are believed to underlie post-action error monitoring. However, it remains elusive how early monitoring activity is trackable and what are the pre-response brain mechanisms related to performance monitoring. Moreover, it is still unclear how task-specific parameters, such as cognitive demand or motor control, influence these processes. Here, we aimed to test pre- and post-error EEG patterns for different types of motor responses and investigate the neuronal mechanisms leading to erroneous actions. We implemented a go/no-go paradigm based on keypresses and saccades. Participants received an initial instruction about the direction of response to be given based on a facial cue and a subsequent one about the type of action to be performed based on an object cue. The paradigm was tested in 20 healthy volunteers combining EEG and eye tracking. We found significant differences in reaction time, number, and type of errors between the two actions. Saccadic responses reflected a higher number of premature responses and errors compared to the keypress ones. Nevertheless, both led to similar EEG patterns, supporting previous evidence for increased ERN amplitude and midfrontal theta power during error commission. Moreover, we found pre-error decreased theta activity independent of the type of action. Source analysis suggested different origin for such pre- and post-error neuronal patterns, matching the anterior insular cortex and the anterior cingulate cortex, respectively. This opposite pattern supports previous evidence of midfrontal theta not only as a neuronal marker of error commission but also as a predictor of action performance. Midfrontal theta, mostly associated with alert mechanisms triggering behavioral adjustments, also seems to reflect pre-response attentional mechanisms independently of the action to be performed. Our findings also add to the discussion regarding how salience network nodes interact during performance monitoring by suggesting that pre- and post-error patterns have different neuronal sources within this network.
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Li-Fraumeni and Li-Fraumeni-like syndromes (LFS/LFL) are hereditary cancer predisposition disorders associated with germline mutations in the TP53 tumor suppressor gene. Here, we stably expressed LFS/LFL-associated p53 mutants R337H and G245S in p53-null H1299 cells to study their cellular and molecular effects. Mutant proteins showed distinct oligomerization states and opposing effects on cell proliferation and viability. Stable expression of p53G245S enhanced cell proliferation and spheroid formation, while cells stably expressing p53R337H showed reduced proliferation and clonogenicity, along with increased cell death. Mass spectrometry analysis revealed that proteins whose expression was induced by p53R337H or p53G245S expression were related to distinct metabolic profiles. Proteins upregulated by p53G245S expression were associated with a Warburg phenotype, while proteins upregulated by p53R337H expression were related to oxidative phosphorylation and fatty acid oxidation. Differences in mitochondrial mass and activity between cells stably expressing p53R337H or p53G245S were further corroborated by High Resolution Respirometry, flow cytometry and qPCR assays. The implications of the different oncogenic properties of p53R337H and p53G245S on the clinical manifestation and treatment of LFS/LFL patients carrying these mutations are discussed.
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Síndrome de Li-Fraumeni , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Humanos , Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/patología , Redes y Vías Metabólicas , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
The risk stratification of B-acute lymphoblastic leukemia (B-ALL) is based on clinical and biological factors. However, B-ALL has significant biological and clinical heterogeneity and 50% of B-ALL patients do not have defined prognostic markers. In this sense, the identification of new prognostic biomarkers is necessary. Considering different cohorts of childhood B-ALL patients, gene (DPP4/CD38/ENTPD1/NT5E) and protein (CD38/CD39/CD73) expressions of ectonucleotidases were analyzed in silico and ex vivo and the association with prognosis was established. In univariate analyses, expression of NT5E was significantly associated with worse progression-free survival (PFS) in bone marrow (BM) samples. In multivariate analyses, Kaplan-Meier analysis, and log-rank test, higher NT5E expression predicted unfavorable PFS in BM samples. Considering minimal residual disease (MRD), higher levels of cellularity were associated with the high NT5E expression at day 8 of induction therapy. In addition, we observed that white blood cells (WBC) of childhood B-ALL patients had more CD38 compared to the same cell population of healthy donors (HD). In fact, MRD > 0.1% patients had higher CD38 protein expression on WBC in comparison to HD. Noteworthy, we observed higher CD38 expression on WBC than blasts in MRD > 0.1% patients. We suggest that NT5E gene and CD38 protein expression, of the ectonucleotidases family, could provide interesting prognostic biomarkers for childhood B-ALL.
Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , 5'-Nucleotidasa/genética , Biomarcadores , Citometría de Flujo , Proteínas Ligadas a GPI , Humanos , Neoplasia Residual/tratamiento farmacológico , Neoplasia Residual/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , PronósticoRESUMEN
Error monitoring is the metacognitive process by which we are able to detect and signal our errors once a response has been made. Monitoring when the outcome of our actions deviates from the intended goal is crucial for behavior, learning, and the development of higher-order social skills. Here, we explored the neuronal substrates of error monitoring during the integration of facial expression cues using electroencephalography (EEG). Our goal was to investigate the signatures of error monitoring before and after a response execution dependent on the integration of facial cues. We followed the hypothesis of midfrontal theta as a robust neuronal marker of error monitoring since it has been consistently described as a mechanism to signal the need for cognitive control. Also, we hypothesized that EEG frequency-domain components might bring advantage to study error monitoring in complex scenarios as it carries information from locked and non-phase-locked signals. A challenging go/no-go saccadic paradigm was applied to elicit errors: integration of facial emotional signals and gaze direction was required to solve it. EEG data were acquired from twenty healthy participants and analyzed at the level of theta band activity during response preparation and execution. Although theta modulation has been consistently demonstrated during error monitoring, it is still unclear how early it starts to occur. We found theta power differences at midfrontal channels between correct and error trials. Theta was higher immediately after erroneous responses. Moreover, before response initiation we observed the opposite: lower theta preceding errors. These results suggest theta band activity not only as an index of error monitoring, which is needed to enhance cognitive control, but also as a requisite for success. This study adds to previous evidence for the role of theta band in error monitoring processes by revealing error-related patterns even before response execution in complex tasks, and using a paradigm requiring the integration of facial expression cues.