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Background: Benfotiamine, a synthetic analog of thiamine, offers greater bioavailability compared to other thiamine salts and increases thiamine stores upon oral intake. Thiamine is essential for energy metabolism. This study aimed to evaluate the effects of oral benfotiamine supplementation on energy metabolism, particularly the Krebs cycle function, in the muscle of endurance-trained mice, and to assess its impact on endurance performance. Methods: Twenty-five mice were randomly assigned to four groups: a standard diet with sedentary behavior (Sta-Sed), a benfotiamine-supplemented diet with sedentary behavior (Ben-Sed), a standard diet with swimming training (Sta-Tr), and a benfotiamine-supplemented diet with swimming training (Ben-Tr). The trained groups underwent five weekly swimming sessions for six weeks, followed by an exhaustive test. Thiamine and its esters were measured in erythrocytes and gastrocnemius muscle. Gene expression of pyruvate dehydrogenase (PDHa) and alpha-ketoglutarate dehydrogenase (OGDH), along with levels of pyruvic, lactic, and hydroxybutyric acids in muscle, was analyzed. Results: The benfotiamine-supplemented groups had higher thiamine levels in erythrocytes and muscles compared to the standard-diet groups. No differences were observed in PDHa and OGDH gene expression. The Ben-Tr group exhibited increased muscle lactic acid levels and a higher lactic acid to pyruvic acid ratio compared to the sedentary groups. Hydroxybutyric acid levels were also elevated in the Ben-Tr group. No significant differences in exhaustive test duration were found between the groups. Conclusion: Benfotiamine supplementation increases thiamine levels in erythrocytes and muscle but does not affect the gene expression of thiamine-dependent enzymes. Although it alters energy metabolism in trained muscle, it does not enhance endurance performance in mice.
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The development of new analgesics has been challenging. Candidate drugs often have limited clinical utility due to side effects that arise because many drug targets are involved in signaling pathways other than pain transduction. Here, we explored the potential of targeting protein-protein interactions (PPIs) that mediate pain signaling as an approach to developing drugs to treat chronic pain. We reviewed the approaches used to identify small molecules and peptide modulators of PPIs and their ability to decrease pain-like behaviors in rodent animal models. We analyzed data from rodent and human sensory nerve tissues to build associated signaling networks and assessed both validated and potential interactions and the structures of the interacting domains that could inform the design of synthetic peptides and small molecules. This resource identifies PPIs that could be explored for the development of new analgesics, particularly between scaffolding proteins and receptors for various growth factors and neurotransmitters, as well as ion channels and other enzymes. Targeting the adaptor function of CBL by blocking interactions between its proline-rich carboxyl-terminal domain and its SH3-domain-containing protein partners, such as GRB2, could disrupt endosomal signaling induced by pain-associated growth factors. This approach would leave intact its E3-ligase functions, which are mediated by other domains and are critical for other cellular functions. This potential of PPI modulators to be more selective may mitigate side effects and improve the clinical management of pain.
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Analgésicos , Transducción de Señal , Humanos , Animales , Analgésicos/farmacología , Analgésicos/química , Transducción de Señal/efectos de los fármacos , Mapas de Interacción de Proteínas/efectos de los fármacos , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/metabolismo , Dolor/metabolismo , Dolor/tratamiento farmacológicoRESUMEN
This study evaluated the efficiency of in vitro culture of preantral follicles (PAF) in a commonly used medium for mesenchymal stem cell (MSC) culture. Parameters assessed included follicle survival, growth, stromal cell density, levels of reduced thiols and reactive oxygen species, epigenetic changes, cell apoptosis, and mRNA abundance. Caprine ovarian tissues were cultured for 1 or 7 days in either PAF or MSC-common media, with uncultured tissues serving as controls. The MSC medium exhibited increased follicular survival and growth and remodeled stromal density potentially through the regulation of oxidative stress and epigenetic changes compared to the PAF medium. In conclusion, our results highlight the importance of the MSC medium in enhancing follicular survival and growth, changing the stromal cell density, as well as in regulating the medium oxidative stress and epigenetic changes during the in vitro culture of caprine PAF.
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Conservation of the genetic diversity through skin and cartilage biobanks represents an essential strategy for maintaining biodiversity. Biobanks for the wild species of the order Rodentia have been little studied. Considering that the cryopreservation technique has specific relationships with the tissue and species of interest, we propose investigating different techniques for preserving tissue integrity and cell viability after cartilage and skin culture from Spix's yellow-toothed cavies. Subsequently, two techniques [solid-surface vitrification (SSV) vs. slow freezing (SF)] were used for cartilage and skin cryopreservation. Tissues not subjected to cryopreservation were used as controls. All tissues were evaluated for morphology and proliferation by histological techniques. Moreover, fragments were cultured, and cells were evaluated for viability, proliferation, metabolism, and apoptosis. Regardless of the cryopreservation technique, no differences were observed for the thickness of the epidermis, dermis, skin, spinous and basal layers, fibroblasts, and proliferative activity regarding the number of nucleolar organizer regions (NOR). SSV ensured better maintenance of epidermal cells, normal chondrocytes, filled gaps, collagen fibers, proliferative activity by NOR area/cell, and reduced perinuclear halos and empty gaps compared to SF. SF ensured the conservation of corneum thickness compared to the control. Although both techniques promoted cell recovery after culture, cells from SF resulted in better subconfluence time and day with cell growth around fragments compared to SSV. In conclusion, both cryopreservation techniques resulted in viable cells after culture. However, SSV promoted better maintenance of tissue morphological integrity, and SF ensured the preservation of all cell quality parameters in Spix's yellow-toothed cavies.
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A differential diet with royal jelly (RJ) during early larval development in honeybees shapes the phenotype, which is probably mediated by epigenetic regulation of gene expression. Evidence indicates that small molecules in RJ can modulate gene expression in mammalian cells, such as the fatty acid 10-hydroxy-2-decenoic acid (10-HDA), previously associated with the inhibition of histone deacetylase enzymes (HDACs). Therefore, we combined computational (molecular docking simulations) and experimental approaches for the screening of potential HDAC inhibitors (HDACi) among 32 RJ-derived fatty acids. Biochemical assays and gene expression analyses (Reverse Transcriptase - quantitative Polymerase Chain Reaction) were performed to evaluate the functional effects of the major RJ fatty acids, 10-HDA and 10-HDAA (10-hydroxy-decanoic acid), in two human cancer cell lines (HCT116 and MDA-MB-231). The molecular docking simulations indicate that these fatty acids might interact with class I HDACs, specifically with the catalytic domain of human HDAC2, likewise well-known HDAC inhibitors (HDACi) such as SAHA (suberoylanilide hydroxamic acid) and TSA (Trichostatin A). In addition, the combined treatment with 10-HDA and 10-HDAA inhibits the activity of human nuclear HDACs and leads to a slight increase in the expression of HDAC-coding genes in cancer cells. Our findings indicate that royal jelly fatty acids collectively contribute to HDAC inhibition and that 10-HDA and 10-HDAA are weak HDACi that facilitate the acetylation of lysine residues of chromatin, triggering an increase in gene expression levels in cancer cells.
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Ácidos Grasos , Inhibidores de Histona Desacetilasas , Simulación del Acoplamiento Molecular , Humanos , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/química , Ácidos Grasos/metabolismo , Abejas , Línea Celular Tumoral , Animales , Ácidos Grasos Monoinsaturados/farmacología , Ácidos Grasos Monoinsaturados/química , Histona Desacetilasa 2/metabolismo , Histona Desacetilasa 2/genética , Histona Desacetilasa 2/antagonistas & inhibidores , Células HCT116RESUMEN
Cellular compartmentalization, achieved through membrane-based compartments, is a fundamental aspect of cell biology that contributes to the evolutionary success of cells. While organelles have traditionally been the focus of research, membrane-less organelles (MLOs) are emerging as critical players, exhibiting distinct morphological features and unique molecular compositions. Recent research highlights the pivotal role of long noncoding RNAs (lncRNAs) in MLOs and their involvement in various cellular processes across different organisms. In the context of cancer, dysregulation of MLO formation, influenced by altered lncRNA expression, impacts chromatin organization, oncogenic transcription, signaling pathways, and telomere lengthening. This review synthesizes the current understanding of lncRNA composition within MLOs, delineating their functions and exploring how their dysregulation contributes to human cancers. Environmental challenges in tumorigenesis, such as nutrient deprivation and hypoxia, induce stress granules, promoting cancer cell survival and progression. Advancements in biochemical techniques, particularly single RNA imaging methods, offer valuable tools for studying RNA functions within live cells. However, detecting low-abundance lncRNAs remains challenging due to their limited expression levels. The correlation between lncRNA expression and pathological conditions, particularly cancer, should be explored, emphasizing the importance of single-cell studies for precise biomarker identification and the development of personalized therapeutic strategies. This article is categorized under: RNA Export and Localization > RNA Localization RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.
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Neoplasias , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Animales , Gránulos Citoplasmáticos/metabolismo , Gránulos Citoplasmáticos/genéticaRESUMEN
The establishment of fibroblast lines enables several applications from the formation of biobanks for the conservation of biodiversity to the use of these cells in physiological and toxicological assays. Considered a species vulnerable to extinction, the characterization of fibroblastic lines of northern tiger cat would contribute to its conservation. Therefore, we established and characterized fibroblasts derived from northern tiger cat during extended passage (third, seventh, and eleventh passages) and cryopreservation with regard to the morphology, viability, apoptotic classification, metabolism, proliferative activity, and oxidative stress by reactive oxygen species (ROS) levels and mitochondrial membrane potential (ΔΨm). Initially, we identified four dermal fibroblast lines by morphology, immunophenotyping, and karyotyping assays. In vitro culture after the third, seventh, and eleventh passages did not affect the viability, apoptotic classification, and ROS levels. Nevertheless, cells at seventh and eleventh passages featured a reduction in metabolism and an alteration in ΔΨm when compared to third passage cells. Additionally, cells at eleventh passage showed changes in the proliferative activity and morphology when compared to other passages. Regarding cryopreservation, no effect was observed on cryopreserved cells for morphology, viability, apoptotic classification, metabolism, and proliferative activity. Nevertheless, cryopreserved cells had alteration for ROS levels and ΔΨm. In summary, fibroblasts from northern tiger cat were affected by extended passage (seventh and eleventh passages) and cryopreservation. Adjustments to the in vitro culture and cryopreservation are necessary to reduce cellular oxidative stress caused by in vitro conditions.
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The efficacy of pregabalin in pain treatment has led to the search for new formulations for its use through different routes of administration. This study aimed to prepare, characterize, and evaluate the cytotoxicity of pregabalin (PG) gels for topical application in the oral cavity. Solutions with three different concentrations of PG were prepared and added to a 1.0% carbopol gel base. Thermal analyses (TG and DSC) and FTIR were performed on the gel and pure pregabalin. Stability (preliminary and accelerated) and rheology studies were also conducted on the gels. Cytotoxicity was evaluated in human gingival fibroblasts in the following groups: WG (1.0% carbopol gel base), PG2G (2.0% pregabalin gel), PG5G (5.0% pregabalin gel), and PG10G (10% pregabalin gel). A transparent and homogeneous gel with a pH of 6 was obtained. The formulations showed stability, and the different drug concentrations did not influence the product's characteristics. None of the tested groups showed cytotoxicity for the analyzed cells. The pregabalin gels exhibited favorable and non-toxic characteristics for human gingival fibroblasts in vitro. Therefore, this product may be a promising therapeutic alternative for topical application in the oral mucosa.
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BACKGROUND & AIMS: Obesity is associated with chronic low-grade inflammation, and adipose tissue inflammation is required for fatty tissue remodeling. Interestingly, immunosuppressed patients, as liver transplant recipients, often experience excessive weight gain. We investigated how liver recipients' inflammatory response affects body weight loss induced by dietary treatment. METHODS: Overweight liver recipients were paired with non-transplanted subjects to compare their peripheral immune profiles. RESULTS: Transplanted patients had similar profiles of peripheral blood mononuclear cells compared to controls but lower CD8lowCD56+CD16+NK cells and higher B lymphocytes. Patients showed lower serum concentrations of IFN-γ, TNF, IL-4, IL-2, and IL-10 and lower inflammatory responsiveness of peripheral blood mononuclear cells under inflammatory stimuli. Liver recipients paired with non-transplanted subjects followed a weight loss dietary plan for 6 months to verify body composition changes. After 3 and 6 months of nutritional follow-up, the control group lost more body weight than the liver recipient group. The control group decreased fat mass and waist circumference, which was not observed in transplanted patients. CONCLUSION: Therefore, liver recipients under immunosuppressant treatment responded less to different inflammatory stimuli. This impaired inflammatory milieu might be implicated in the lack of response to weight loss dietary intervention. Inflammation may be essential to trigger the weight loss induced by dietary prescription. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov identification number: NCT03103984.
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Dieta Reductora , Inflamación , Trasplante de Hígado , Pérdida de Peso , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Composición Corporal , Citocinas/sangre , Dieta Reductora/métodos , Inmunosupresores/administración & dosificación , Inflamación/sangre , Leucocitos Mononucleares/inmunología , Obesidad/dietoterapia , Obesidad/cirugía , Obesidad/inmunología , Sobrepeso/dietoterapia , Sobrepeso/inmunología , Sobrepeso/complicacionesRESUMEN
Introdução:A inserção das equipes de saúde bucal na Estratégia Saúde da Família, embora tardia, representa um avanço significativo para a ampliação da cobertura e da qualidade dos serviços odontológicos no Brasil. No entanto, aindaexistem muitosdesafiosnas práticas do cirurgião-dentista na Estratégia Saúde da Família. A atuação majoritariamente clínica prejudica a realização deum trabalho humanístico, resolutivo, interdisciplinar e multiprofissional. Objetivo:Relatar a experiência de atuação de uma cirurgiã-dentista residente na Atenção Primária em Saúde no município de Santo Estêvão, Bahia, Brasil, durante o Programa de Residência Multiprofissional em Saúde da Família da Universidade Estadual de Feira de Santana. Metodologia:Trata-se de um estudo qualitativo, do tipo relato de experiência, que visa descrever as atividades desenvolvidas durante o Programa de Residência Multiprofissional em Saúde da Família, da Universidade Estadual de Feira de Santana, no município de Santo Estêvão, Bahia, Brasil, no período de março de 2022 a novembro de 2023. Resultados:As atividades descritas abrangem as diferentes possibilidades de trabalho do cirurgião-dentista na Atenção Primária, envolvendo ações assistenciais através das consultas individuais e levantamento epidemiológico, educação permanente e em saúde com atuação nos grupos operativos e capacitações com os profissionais da rede e as ações de planejamento e gestão, através do desenvolvimento de estratégias para fortalecer a rede de atenção à saúde. Conclusões:É preciso motivar os profissionais de saúde bucal a repensarem suas práticas, tendo como ponto de partida o investimento e o estímulo à educação permanente e continuada. A especialização em saúde da família permite que cirurgiões-dentistas que atuam ou têminteresse em trabalhar no serviço público desenvolvam habilidades e práticas voltadas para uma assistência integral e multiprofissional da saúde, contribuindo para a consolidação do Sistema Único de Saúde (AU).
Introduction:The oral health team inclusion in the Family Health Strategy represents a significant advance in expanding the coverage and quality of dental services in Brazil. However, there arestill many challenges in the dental surgeons practices in the Family Health Strategy. The ppredominantly clinical approach hinders the achievement of ahumanistic, problem-solving, and interdisciplinary and multidisciplinary. Objective:To report the experience of a dental surgeon resident in Primary Health Care in the city of Santo Estêvão, Bahia, Brazil, during the Multidisciplinary Residency Program in Family Health at the Universidade Estadual de Feira de Santana. Methodology:This is a qualitative study, experience report type, which aims to describe the activities developed during the Multidisciplinary Residency Program in Family Health at the Universidade Estadual de Feira de Santana, in the city of Santo Estêvão, Bahia, Brazil, from March 2022 to November 2023. Results:The activities described cover the different work possibilities of dental surgeons in Primary Care, involving assistance actions through individual consultations and epidemiological surveys, ongoing health education with work in operative groups and training with network professionals, and planning and management actions through the development of strategies to strengthen the health care network. Conclusion:It is necessary to motivate oral health professionals to rethink their practices, with investment and encouragement for permanent and continuing education as a starting point. Specialization in family health allows dental surgeons who work or are interested in working in the public service to develop skills and practices aimed at comprehensive and multidisciplinary health care, contributing to the consolidation of the Unified Health System (AU).
Introducción: La inclusión de los equipos de salud dental en la Estrategia de Salud Familiar, aunque tardía, representa un avance significativo en la ampliación de la cobertura y la calidad de los servicios dentales en Brasil. Sin embargo, los cirujanos dentistas siguen enfrentándose a muchos retos em la Estrategia de Salud Familiar. El enfoque mayoritariamente clínico obstacualiza la realización de um enfoque humanista, resolutivo, interdisciplinario y multiprofesional.Objetivo:Reportar la experiencia de un cirujano dentista residente en Atención Primaria de Salud en el ayuntamiento de Santo Estêvão, Bahía, Brasil, durante el Programa de Residencia Multiprofesional en Salud Familiar de la Universidad Estadual de Feira de Santana.Metodología:Se trata de un estudio cualitativo, del tipoinforme de experiencia, que tiene como objetivo describir las actividades desarrolladas durante el Programa de Residencia Multiprofesional en Salud Familiar de la Universidad Estadual de Feira de Santana, en el ayuntamiento de Santo Estêvão, Bahía, Brasil, de marzo de 2022 a noviembre de 2023. Resultados:Las actividades descritas abarcan las diferentes posibilidades de trabajo del cirujano dentista en la Atención Primaria, implicando actividades asistenciales mediante consultas individuales y encuestas epidemiológicas, educación sanitaria continuada con actuación en los grupos operativos y capacitaciones con los profesionales de la red y actividades de planificación y gestión mediante el desarrollo de estrategias de fortalecimiento de la red de atención sanitaria.Conclusiones:Es necesario motivar a los profesionales de la salud dental a replantear sus prácticas, con la inversión y el fomento de la formación permanente y continua como punto de partida. La especialización en salud familiar permite a los cirujanos dentistas que trabajan o están interesados en trabajar en el servicio público desarrollar competencias y prácticas dirigidas a la atención sanitaria integral y multiprofesional, contribuyendo a la consolidación del Sistema Único de Salud (AU).
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Humanos , Femenino , Atención Odontológica , Odontólogos , Equipo de Atención Dental , Internado y Residencia , Atención Primaria de Salud , Estrategias de Salud Nacionales , Investigación CualitativaRESUMEN
Both Candida albicans and Issatchenkia orientalis have been isolated from different types of infections over the years. They have the ability to form communities of microorganisms known as biofilms. It has been demonstrated that the medium employed in studies may affect the biofilm development. The aim of this study was to investigate the arrangement of dual-species biofilms of C. albicans and I. orientalis cultivated on either RPMI-1640 or Sabouraud Dextrose Broth (SDB), as well as the inhibitory effect of Voriconazole (VRC). For the experiments performed, ATCC strains were used, and yeast-mixed suspensions were inoculated in 96-well plates with either RPMI-1640 or SDB, in the presence or absence of VRC. The results were observed by counting the number of CFU obtained from scraping off the biofilms produced and plating the content on CHROMagar Candida medium. It was observed that for all conditions tested the medium chosen affected the arrangement of dual-species biofilms: when RPMI-1640 was used, there was a prevalence of C. albicans, while the opposite was noted when SDB was used. It could be suggested that the medium and environment could regulate interactions between both yeast species, including the response to different antifungal drugs.
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Antifúngicos , Biopelículas , Candida albicans , Medios de Cultivo , Voriconazol , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Voriconazol/farmacología , Candida albicans/efectos de los fármacos , Candida albicans/fisiología , Antifúngicos/farmacología , Medios de Cultivo/química , Saccharomycetales/efectos de los fármacos , Saccharomycetales/fisiología , Pruebas de Sensibilidad MicrobianaRESUMEN
Mammalian Ste-20-like Kinases 1 and 2 (MST1/2) are core serine-threonine kinases of the Hippo pathway regulating several cellular processes, including cell cycle arrest and cell death. Here, we discovered a novel alternative splicing variant of the MST2 encoding gene, STK3, in malignant cells and tumor datasets. This variant, named STK3∆7 or MST2∆7 (for mRNA or protein, respectively), resulted from the skipping of exon 7. MST2∆7 exhibited increased ubiquitylation and interaction with the E3 ubiquitin-protein ligase CHIP compared to the full-length protein (MST2FL). Exon 7 in STK3 encodes a segment within the kinase domain, and its exclusion compromised MST2 interaction with and phosphorylation of MOB, a major MST1/2 substrate. Nevertheless, MST2∆7 was capable of interacting with MST1 and MST2FL. Unlike MST2FL, overexpression of MST2∆7 did not lead to increased cell death and growth arrest. Strikingly, we observed the exclusion of STK3 exon 7 in 3.2-15% of tumor samples from patients of several types of cancer, while STK3∆7 was seldomly found in healthy tissues. Our study identified a novel STK3 splicing variant with loss of function and the potential to disturb tissue homeostasis by impacting on MST2 activities in the regulation of cell death and quiescence.
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Empalme Alternativo , Proliferación Celular , Proteínas Serina-Treonina Quinasas , Serina-Treonina Quinasa 3 , Humanos , Proteínas Adaptadoras Transductoras de Señales , Línea Celular Tumoral , Exones/genética , Células HEK293 , Factor de Crecimiento de Hepatocito/genética , Factor de Crecimiento de Hepatocito/metabolismo , Neoplasias/genética , Neoplasias/patología , Neoplasias/metabolismo , Fosforilación , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Serina-Treonina Quinasa 3/genética , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación/genéticaRESUMEN
Integrating agricultural, chemical, and technological knowledge is crucial for developing bio-nanotechnologies to improve agricultural production. This study explores the innovative use of biopolymeric coatings, based on sodium alginate and sodium alginate + Laponite® (nanoclay), containing biostimulants (tryptophol and thymol) or not, on garlic cloves. These coatings were analyzed using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR-ATR), and scanning electron microscopy (SEM). Greenhouse bioassays showed improvements in garlic shoot plant biomass with both treatments: sodium alginate biopolymer and sodium alginate biopolymer plus Laponite®. In the field experiment, garlic plants treated with sodium alginate, in combination with conventional pesticide treatments, resulted in better quality garlic bulbs, where larger garlics were harvested in this treatment, reducing commercial losses. In tropical garlic crops, obtaining plants with greater initial vigor is essential. Our results highlight the potential of these bio-nanotechnological strategies to enhance garlic propagation, ensuring environmental protection and food security.
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Ajo , Ajo/química , Biopolímeros/química , Alginatos/química , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X , Microscopía Electrónica de Rastreo , Nanotecnología/métodosRESUMEN
Floodplains contribute significantly to terrestrial ecosystem service provision but are also among the most vulnerable and degraded ecosystems worldwide. Heterogeneity in floodplain properties arises from variations in river-specific flood regimes, watershed characteristics, and valley morphology, influencing seasonally flooded forests' taxonomic, functional, and phylogenetic diversity. This study addresses persisting knowledge gaps in floodplain ecology, focusing on the seasonally dry tropics. We explore the relationships between flood regime, environmental conditions, vegetation composition, functional and phylogenetic diversity, and the impact of environmental variables on above-ground biomass (AGB) and ecological strategies. The study spans six rivers in southeastern Brazil's main river basins: Rio Grande and São Francisco. We identified five eco-units in each floodplain based on flooding regimes and surveyed six plots per eco-unit. We measured trees with DBH > 5 cm and collected functional traits, along with detailed soil, climate, and water level data. We calculated plot-level floristic composition, taxonomic, functional, and phylogenetic diversity, wood density, and AGB. Functional and phylogenetic dissimilarity were analyzed, and the effects of climate, soil, and hydrological variables were quantified using generalized linear mixed models. We show how flood frequency and duration affect floristic composition across the floodplains. Taxonomic and phylogenetic diversity responded to climate, soil, and hydrological variables, while functional diversity responded primarily to hydrological variables, emphasizing the role of environmental filtering. Hydrological seasonality, soil fertility, and flood regime emerged as key factors shaping community structure and ecological strategies in the studied seasonally flooded tropical forests. Plot-level AGB responded to phosphorus but not to climate or hydrological variables. The study also highlights functional and phylogenetic dissimilarities among eco-units and basins, indicating potential climate change impacts.
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Biodiversidad , Inundaciones , Bosques , Filogenia , Brasil , Clima Tropical , Estaciones del Año , Monitoreo del Ambiente , EcosistemaRESUMEN
The local field potential (LFP) is as a measure of the combined activity of neurons within a region of brain tissue. While biophysical modeling schemes for LFP in cortical circuits are well established, there is a paramount lack of understanding regarding the LFP properties along the states assumed in cortical circuits over long periods. Here we use a symbolic information approach to determine the statistical complexity based on Jensen disequilibrium measure and Shannon entropy of LFP data recorded from the primary visual cortex (V1) of urethane-anesthetized rats and freely moving mice. Using these information quantifiers, we find consistent relations between LFP recordings and measures of cortical states at the neuronal level. More specifically, we show that LFP's statistical complexity is sensitive to cortical state (characterized by spiking variability), as well as to cortical layer. In addition, we apply these quantifiers to characterize behavioral states of freely moving mice, where we find indirect relations between such states and spiking variability.
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Modelos Neurológicos , Corteza Visual Primaria , Animales , Ratones , Ratas , Corteza Visual Primaria/fisiología , Corteza Visual Primaria/citología , Potenciales de Acción , Neuronas/fisiología , Corteza Visual/fisiología , Corteza Visual/citologíaRESUMEN
Acute myeloid leukaemia (AML) is a lethal bone marrow neoplasm caused by genetic alterations in blood cell progenitors. Leukaemic stem cells (LSCs) are responsible for the development of AML, drug resistance and relapse. Bithionol is an old anthelmintic drug with potential antibacterial, antiviral, antifungal, anti-Alzheimer, and antitumour properties. In this work, we focused on the anti-AML LSC properties of bithionol. This compound inhibited the viability of both solid and haematological cancer cells, suppressed AML stem-like cells, and inhibited AML growth in NSG mice at a dosage of 50 mg/kg, with tolerable systemic toxicity. Bithionol significantly reduced the levels of phospho-NF-κB p65 (Ser529) and phospho-NF-κB p65 (Ser536) and nuclear NF-κB p65 translocation in AML cells, indicating that this molecule can suppress NF-κB signalling. DNA fragmentation, nuclear condensation, cell shrinkage, phosphatidylserine externalisation, loss of transmembrane mitochondrial potential, caspase-3 activation and PARP-(Asp 214) cleavage were detected in bithionol-treated AML cells, indicating the induction of apoptosis. Furthermore, this compound increased mitochondrial superoxide levels, and bithionol-induced cell death was partially prevented by cotreatment with the selective ferroptosis inhibitor ferrostatin-1, indicating the induction of ferroptosis. In addition, bithionol synergised with venetoclax in AML cells, indicating the translational potential of bithionol to enhance the effects of venetoclax in patients with AML. Taken together, these data indicate that bithionol is a potential new anti-AML drug.
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Blood transfusion is a life-saving procedure widely used in healthcare. However, complications such as transfusion reactions may occur. Knowledge of these reactions is essential for patient safety. Nurses play a crucial role in this process by identifying complications and adverse reactions early on. A lack of professional competence in blood transfusion can lead to errors and serious complications, such as death. The aim of this study was to present evidence of the content validity of a simulated clinical scenario on transfusion reactions for teaching and learning for nursing students. This methodological study was carried out in three phases: (1) development of the simulated scenario of a transfusion reaction; (2) analysis of evidence of content validity by experts (n = 11); and (3) determination of satisfaction and self-confidence in the use of the simulated scenario by the nursing students (n = 45). The Content Validity Index was 94%. After the scenario had been developed, the content was validated and approved by 100% of the experts. All the items in the simulated scenario obtained agreement scores above 0.90. The simulated scenario was validated in terms of content and can be used to teach the management of transfusion reactions.
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Estudiantes de Enfermería , Reacción a la Transfusión , Humanos , Reacción a la Transfusión/prevención & control , Educación en Enfermería/métodos , Femenino , Masculino , Adulto , Entrenamiento Simulado , Adulto Joven , Competencia Clínica , Transfusión SanguíneaRESUMEN
Lung carcinoids are rare tumors representing 1-2% of all invasive lung malignancies. They include typical and atypical carcinoids, whose distinction is made based on the mitotic index and presence or absence of necrosis. The 10-year overall survival for stage IV typical carcinoid is 47% and 18% for atypical carcinoid, reflecting the indolent growth of these tumors. There are limited approved treatment options for them and most of the evidence comes from retrospective analyses, single-arm trials, subgroup analysis of phase II/III trials for metastatic neuroendocrine tumors and extrapolation of data from phase III trials for gastroenteropancreatic neuroendocrine tumors. Management of metastatic lung carcinoids requires a multidisciplinary standardized approach in specialized centers. Treatment should have a dual objective, control of tumor growth and control of symptoms related to hypersecretion syndromes, aiming to improve quality of life and survival. In the continuum of treatment disease, locoregional treatment options need to be considered in parallel with systemic treatments. In this paper, we review the present treatment options and their rational and we give an insight into future alternatives.
RESUMEN
We evaluated the influence of different media plus various concentrations of Glial cell line-derived neurotrophic factor (GDNF) during the in vitro culture (IVC) of testicular tissues from prepubertal collared peccary. Testes from 5 individuals were collected, fragmented and cultured for 28 days (34°C and 5% CO2). Culture media were Dulbecco's modified essential medium (DMEM) or stem cell serum free media (StemPro-34™ SFM), both supplemented with various concentrations of GDNF (0, 10, or 20 ng/mL). Fragments were cultured on the flat surface of 0.75% agarose gel and were evaluated every 7 days for fragment area, histomorphology, cellular viability, and proliferative activity. Data were expressed as mean ± standard error and analyzed by Kruskal-Wallis's and Tukey test. Fragments area decreased over the 28 days-culture, regardless of the treatment. For morphology, the StemPro-37 SFM medium plus 10 ng/mL GDNF provided higher scores at all time points in comparison to DMEM using any GDNF concentration (p < .05). After 28 days, similar cellular viability (~70%) was observed in all treatments (p > .05). For proliferating cell nuclear antigen assay, only DMEM plus 10 ng/mL GDNF improved (p < .05) cellular proliferation on Days 14 and 28. Looking at argyrophilic nucleolar organizing regions, after 28 days, there were no differences among treatments regarding cell proliferative capacity for both spermatogonia and Sertoli cells (p > .05). In summary, the DMEM and StemPro-34 SFM are adequate medium for IVC of prepubertal peccary testicular tissue. Supplementation with GDNF, especially at a 10 ng/mL concentration, appears to be essential for the maintenance of cell survival and proliferation.