RESUMO
BACKGROUND: The current study mainly focused on provide further insights into the association of the miR-22-3p and miR-29c-3p expression in CFU-Hill colonies with birth weight and senescence process in children. METHODS: This cross-sectional study evaluated 61 children (32 boys, 29 girls). The CFU-Hill colonies number was evaluated in vitro by cell culture technique and senescence was detected by ß-galactosidase (SA-ß-Gal) assay. Expression of miR-22-3p and miR-29c-3p isolated from CFU-Hill colonies were detected using quantitative real-time polymerase chain reaction. RESULTS: Birth weight was correlated with both CFU-Hill colonies and %SA-ß-Gal positive staining. Multivariate linear regression analysis revealed that the senescence was a predictor of the lower CFU-Hill colonies number, while only the birth weight was a predictor of senescence of CFU-Hill colonies. Overexpression of miR-22-3p and miR-29c-3p was observed in CFU-Hill colonies isolated from children with low birth weight (LBW). Interestingly, we found a significant correlation between %SA-ß-Gal cells staining positive for both miR-22-3p and miR-29c-3p. CONCLUSION: The LBW is associated with decreased CFU-Hill colonies number and high senescence of these cells. The overexpression of miR-22-3p and miR-29c-3p may be partially responsible for this alteration due to regulation of several pathways related to the senescence process. IMPACT: The study establishes a significant correlation between birth weight and the number of CFU-Hill colonies, suggesting that birth weight could be a predictive biomarker for vascular health in children. Data indicates that cellular senescence is a predictor of reduced CFU-Hill colony numbers. This suggests that the aging process of these cells could be an important factor in understanding the vascular health issues in children with low birth weight. The overexpression of miR-22-3p and miR-29c-3p in children with low birth weight and their correlation with increased cellular senescence highlight these microRNAs as possible molecular mechanisms influencing the aging of CFU-Hill colonies.
Assuntos
Senescência Celular , Recém-Nascido de Baixo Peso , MicroRNAs , Humanos , MicroRNAs/metabolismo , MicroRNAs/genética , Feminino , Masculino , Estudos Transversais , Recém-Nascido , Peso ao Nascer , beta-Galactosidase/metabolismo , Ensaio de Unidades Formadoras de Colônias , Lactente , Pré-EscolarRESUMO
Foraging is a behavioural process and, therefore, individual behaviour and diet are theorized to covary. However, few comparisons of individual behaviour type and diet exist in the wild. We tested whether behaviour type and diet covary in a protected population of Atlantic cod, Gadus morhua. Working in a no-take marine reserve, we could collect data on natural behavioural variation and diet choice with minimal anthropogenic disturbance. We inferred behaviour using acoustic telemetry and diet from stable isotope compositions (expressed as δ13 C and δ15 N values). We further investigated whether behaviour and diet could have survival costs. We found cod with shorter diel vertical migration distances fed at higher trophic levels. Cod δ13 C and δ15 N values scaled positively with body size. Neither behaviour nor diet predicted survival, indicating phenotypic diversity is maintained without survival costs for cod in a protected ecosystem. The links between diet and diel vertical migration highlight that future work is needed to understand whether the shifts in this behaviour during environmental change (e.g. fishing or climate), could lead to trophic cascades.
Assuntos
Ecossistema , Gadus morhua , Animais , Clima , Isótopos , Comportamento EspacialRESUMO
We used nanopore sequencing and phylogenetic analyses to identify a cosmopolitan genotype of dengue virus serotype 2 that was isolated from a 56-year-old male patient from the state of Goiás in Brazil. The emergence of a cosmopolitan genotype in Brazil will require risk assessment and surveillance to reduce epidemic potential.
Assuntos
Vírus da Dengue , Dengue , Brasil/epidemiologia , Dengue/epidemiologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , SorogrupoRESUMO
Due to an increasing demand for sustainable agricultural practices, the adoption of microbial volatile organic compounds (VOCs) as antagonists against phytopathogens has emerged as an eco-friendly alternative to the use of agrochemicals. Here, we identified three Pseudomonas strains that were able to inhibit, in vitro, up to 80% of mycelial growth of the phytopathogenic fungus Thielaviopsis ethacetica, the causal agent of pineapple sett rot disease in sugarcane. Using GC/MS, we found that these bacteria produced 62 different VOCs, and further functional validation revealed compounds with high antagonistic activity to T. ethacetica. Transcriptomic analysis of the fungal response to VOCs indicated that these metabolites downregulated genes related to fungal central metabolism, such as those involved in carbohydrate metabolism. Interestingly, genes related to the DNA damage response were upregulated, and micro-FTIR analysis corroborated our hypothesis that VOCs triggered DNA damage. Electron microscopy analysis showed critical morphological changes in mycelia treated with VOCs. Altogether, these results indicated that VOCs hampered fungal growth and could lead to cell death. This study represents the first demonstration of the molecular mechanisms involved in the antagonism of sugarcane phytopathogens by VOCs and reinforces that VOCs can be a sustainable alternative for use in phytopathogen biocontrol.
Assuntos
Ascomicetos , Saccharum , Compostos Orgânicos Voláteis , Ascomicetos/metabolismo , Bactérias/metabolismo , Dano ao DNA , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/farmacologiaRESUMO
Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barré syndrome. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains absent. Here we demonstrate that ZIKV(BR) infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKV(BR) outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human neurodevelopment.
Assuntos
Modelos Animais de Doenças , Microcefalia/virologia , Zika virus/patogenicidade , Animais , Apoptose , Autofagia , Encéfalo/patologia , Encéfalo/virologia , Brasil/epidemiologia , Proliferação de Células , Feminino , Retardo do Crescimento Fetal/patologia , Retardo do Crescimento Fetal/virologia , Feto/virologia , Camundongos , Microcefalia/epidemiologia , Microcefalia/etiologia , Microcefalia/patologia , Células-Tronco Neurais/patologia , Células-Tronco Neurais/virologia , Organoides/patologia , Organoides/virologia , Placenta/virologia , Gravidez , Infecção por Zika virus/complicações , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/patologia , Infecção por Zika virus/virologiaRESUMO
The indiscriminate utilization of agrochemicals causes environmental and animal life impacts. In this regard, methodologies have been developed to offer efficiency and quickness for agrochemicals detection. Due to their selectivity and molecular recognition sites, Molecular Imprinted Polymer (MIPs) have been widely employed in some areas, including biotechnology, waste analyses, foodstuff, biological fluids, and others. This work proposed developing a method to determine aminocarb, pirimicarb, dimethoate, omethoate, pyridaphenthion, and fenitrothion pesticides using molecularly imprinted polymer combined with solid-phase extraction (MIP-SPE) for clean-up and paper spray ionization mass spectrometry for their analysis. Extractions analysis for Aminocarb, Pirimicarb, and Omethoate using MIP-SPE showed better performance when compared with MIP and NIP. The R 2 values were found with R 2 > 0.98 for all pesticides, and LODs and LOQs values were 50 and 100 µg kg-1, respectively. The precision and accuracy were assessed at three concentration levels-low, medium, and high. The precision values (interday and intraday) were below 10%, and the variation of recovery was between 80 and 120% for all pesticides. Therefore, it was possible to verify the presence of two carbamates and five organophosphorus without the necessity of preconcentration samples with precision and good recovery. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05464-7.
RESUMO
Cellular therapy with mesenchymal stem cells (MSCs) is a huge challenge for scientists, as little translational relevance has been achieved. However, many studies using MSCs have proved their suppressive and regenerative capacity. Thus, there is still a need for a better understanding of MSCs biology and the establishment of newer protocols, or to test unexplored tissue sources. Here, we demonstrate that murine endometrial-derived MSCs (meMSCs) suppress Experimental Autoimmune Encephalomyelitis (EAE). MSC-treated animals had milder disease, with a significant reduction in Th1 and Th17 lymphocytes in the lymph nodes and in the central nervous system (CNS). This was associated with increased Il27 and Cyp1a1 expression, and presence of IL-10-secreting T CD4+ cells. At EAE peak, animals had reduced CNS infiltrating cells, histopathology and demyelination. qPCR analysis evidenced the down-regulation of several pro-inflammatory genes and up-regulation of indoleamine-2,3-dioxygenase (IDO). Consistently, co-culturing of WT and IDO-/- meMSCs with T CD4+ cells evidenced the necessity of IDO on the suppression of encephalitogenic lymphocytes, and IDO-/- meMSCs were not able to suppress EAE. In addition, WT meMSCs stimulated with IL-17A and IFN-γ increased IDO expression and secretion of kynurenines in vitro, indicating a negative feedback loop. Pathogenic cytokines were increased when CD4+ T cells from AhR-/- mice were co-cultured with WT meMSC. In summary, our research evidences the suppressive activity of the unexplored meMSCs population, and shows the mechanism depends on IDO-kynurenines-Aryl hydrocarbon receptor (AhR) axis. To our knowledge this is the first report evidencing that the therapeutic potential of meMSCs relying on IDO expression.
Assuntos
Encefalomielite Autoimune Experimental/terapia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Transplante de Células-Tronco Mesenquimais , Animais , Encefalomielite Autoimune Experimental/enzimologia , Encefalomielite Autoimune Experimental/imunologia , Endométrio/citologia , Feminino , Ativação Linfocitária , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Camundongos Endogâmicos C57BL , Linfócitos T/metabolismoRESUMO
Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.
Assuntos
Doenças do Sistema Nervoso , Infecção por Zika virus , Zika virus , Animais , Feminino , Humanos , Camundongos , Placenta , Gravidez , Replicação Viral , Infecção por Zika virus/complicaçõesRESUMO
Understanding the responses of aquatic animals to temperature variability is essential to predict impacts of future climate change and to inform conservation and management. Most ectotherms such as fish are expected to adjust their behaviour to avoid extreme temperatures and minimize acute changes in body temperature. In coastal Skagerrak, Norway, sea surface temperature (SST) ranges seasonally from 0 to over 20°C, representing a challenge to the fish community which includes cold-, cool- and warm-water affinity species. By acoustically tracking 111 individuals of Atlantic cod Gadus morhua, pollack Pollachius pollachius and ballan wrasse Labrus bergylta in 2015-2018, we examined how coexisting species within a fish community adjusted their behaviour (i.e. vertical distribution in the water column and habitat selection) to cope with the thermal variation. Mixed-effect models showed that thermal preference was a main driver of behaviour and habitat use of the fish community in a southern Norwegian fjord. Cod used colder waters, compared with pollack and ballan wrasse. Increases in SST during summer were associated with the use of deeper, colder waters by cod, especially by larger individuals, and conversely with the occupancy of shallower areas by pollack and ballan wrasse. During winter, when SST dropped and the thermal stratification reversed, pollack and ballan wrasse moved to deeper, relatively warmer areas, while cod selected shallower, colder habitats. Although habitat selection was affected by temperature, species-specific habitat selection was observed even when temperature was similar throughout habitats. This study shows how cohabiting fish species respond to thermal heterogeneity, suggesting that (a) temperature regulates the access to the different depths and habitats and (b) behavioural plasticity may be an important factor for coping with temperature variability and potentially for adaptation to climate change.
Assuntos
Ecossistema , Gadus morhua , Animais , Peixes , Noruega , TemperaturaRESUMO
INTRODUCTION: Androgen deprivation therapy (ADT) is the mainstay of therapy for advanced prostate cancer. Studies addressing the efficacy of different depot formulations of long acting luteinizing hormone releasing hormone agonists in the Brazilian population are lacking. We aimed to compare the efficacy of three schedules of leuprolide acetate in lowering PSA in a real world population. MATERIALS AND METHODS: We reviewed the medical records of patients with prostate cancer seen at our institution between January 2007 and July 2018. We analyzed patients treated with long-acting leuprolide acetate and grouped these patients into three strata according to the administration of ADT every 1, 3 or 6 months. The primary outcome was the serum prostate specific antigen (PSA) levels at 6 and 12 months after treatment initiation. We used Friedman test to compare the distribution of PSA levels at baseline and at 6 and 12 months within each treatment stratum. We considered two-sided P values < 0.05 as statistically significant. We analyzed toxicity descriptively. RESULTS: We analyzed a total of 932 patients, with a median age of 72 years and a median time since diagnosis of prostate cancer of 8.5 months. ADT was administered monthly in 115 patients, quarterly in 637, and semiannually in 180. Nearly half of the patients had locally advanced disease. In comparison with baseline, median serum PSA levels were reduced at 12 months by at least 99.7% in the three strata (P < 0.001 in all cases). Sexual impotence and hot flashes were the most frequently reported toxicities. CONCLUSION: To our knowledge, this is the largest assessment of real-world data on alternative schedules of leuprolide in a Brazilian population. Our study suggests that PSA levels can be effectively be reduced in most patients treated with monthly, quarterly, or semiannual injections of long-acting leuprolide acetate.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Leuprolida/uso terapêutico , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata , Acetatos , Idoso , Antagonistas de Androgênios , Brasil , Humanos , Masculino , Estudos RetrospectivosRESUMO
Genetic divergence among populations arises through natural selection or drift and is counteracted by connectivity and gene flow. In sympatric populations, isolating mechanisms are thus needed to limit the homogenizing effects of gene flow to allow for adaptation and speciation. Chromosomal inversions act as an important mechanism maintaining isolating barriers, yet their role in sympatric populations and divergence with gene flow is not entirely understood. Here, we revisit the question of whether inversions play a role in the divergence of connected populations of the marine fish Atlantic cod (Gadus morhua), by exploring a unique data set combining whole-genome sequencing data and behavioural data obtained with acoustic telemetry. Within a confined fjord environment, we find three genetically differentiated Atlantic cod types belonging to the oceanic North Sea population, the western Baltic population and a local fjord-type cod. Continuous behavioural tracking over 4 year revealed temporally stable sympatry of these types within the fjord. Despite overall weak genetic differentiation consistent with high levels of gene flow, we detected significant frequency shifts of three previously identified inversions, indicating an adaptive barrier to gene flow. In addition, behavioural data indicated that North Sea cod and individuals homozygous for the LG12 inversion had lower fitness in the fjord environment. However, North Sea and fjord-type cod also occupy different depths, possibly contributing to prezygotic reproductive isolation and representing a behavioural barrier to gene flow. Our results provide the first insights into a complex interplay of genomic and behavioural isolating barriers in Atlantic cod and establish a new model system towards an understanding of the role of genomic structural variants in adaptation and diversification.
Assuntos
Inversão Cromossômica/genética , Gadus morhua/genética , Fluxo Gênico/genética , Seleção Genética/genética , Animais , Deriva Genética , Aptidão Genética/fisiologia , Variação Genética/genética , Homozigoto , Isolamento Reprodutivo , Simpatria/genéticaRESUMO
OBJECTIVE: To validate the defining characteristics of the nursing diagnosis "labile emotional control" in traumatic brain injury (TBI) outpatients. DESIGN: This was a descriptive, cross-sectional, quantitative study. METHODS: Thirty-one Brazilian nurses who were experts in the area of TBI answered a semistructured questionnaire on the diagnosis "labile emotional control" based on NANDA-International (NANDA-I) Taxonomy II (2015-2017) using a Likert-type scale to rate the 13 defining characteristics. Based on Fehring's model, the weighted average of ≥80 was used to define the main characteristic and the mean of ≥0.50 was considered for total content validation. RESULTS: Out of the 13 defining characteristics of the nursing diagnosis studied, "leaving a social situation" (0.80) and "expression of emotions inconsistent with the triggering factor" (0.81) were classified as principal characteristics, while the 11 others were classified as secondary characteristics. The diagnosis "labile emotional control" obtained a total score of 0.69, which was considered valid according to NANDA-I Taxonomy II. CONCLUSIONS: Because this is a new diagnosis with subjective characteristics, there is a need to train nurses to recognize the defining characteristics for the diagnosis. CLINICAL RELEVANCE: The validation of this diagnosis helps nurses understand and identify the subjective characteristics of the emotional impressions expressed by patients with TBI. These defining characteristics will help improve TBI nurses' clinical practice.
Assuntos
Sintomas Afetivos/diagnóstico , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/psicologia , Emoções , Diagnóstico de Enfermagem/métodos , Diagnóstico de Enfermagem/normas , Sintomas Afetivos/etiologia , Brasil , Estudos Transversais , Humanos , Índice de Gravidade de Doença , Inquéritos e Questionários , Terminologia como AssuntoRESUMO
Although growing evidence supports the idea that animal personality can explain plasticity in response to changes in the social environment, it remains to be tested whether it can explain spatial responses of individuals in the face of natural environmental fluctuations. This is a major challenge in ecology and evolution as spatial dynamics link individual- and population-level processes. In this study, we investigated the potential of individual personalities to predict differences in fish behaviour in the wild. Specifically, our goal was to answer if individual differences in plasticity of space use to sea surface temperature could be explained by differences in personality along the reactive-proactive axis. To address this question, we first conducted repeated standard laboratory assays (i.e., open-field test, novel object test and mirror stimulation test) to assess the personality type of 76 wild-caught Atlantic cod (Gadus morhua). Next, we released the fish back into the sea and monitored their spatial behaviour over large temporal (16 months) and spatial (a whole fjord) scales, using high-resolution acoustic tracking. We demonstrate that (a) cod personality traits are structured into a proactive-reactive syndrome (proactive fish being more bold, exploratory and aggressive), (b) mean depth use of individuals is mainly driven by sea temperature and (c) personality is a significant predictor of home range changes in the wild, where reactive, but not proactive, individuals reduced their home range as sea temperature increased. These findings expand our understanding of the ecological consequences of animal personality and the mechanisms shaping spatial dynamics of animals in nature.
Assuntos
Peixes , Gadus morhua , Animais , Comportamento Animal , Ecologia , Comportamento de Retorno ao Território Vital , PersonalidadeRESUMO
BACKGROUND: Cardiovascular diseases are the leading cause of death globally and sedentary lifestyle is one of the main risk factors. Home-based cardiac rehabilitation (CR) programs appear to be effective to improve exercise tolerance. The aim of the study, therefore, was to evaluate the effects of a phase IV (maintenance) home-based CR program on cardiorespiratory fitness and daily physical activity of patients recovering from an acute myocardial infarction. METHODS: This pilot study, with a sub-group randomised controlled trial, included 32 individuals recovering from a myocardial infarction, randomly divided into the experimental group (EG, n=16) and the control group (CG, n=16). The EG performed an exercise program, three times per week, at home during eight weeks. The two groups received health education sessions. Baseline and final assessments included cardiorespiratory fitness, resting and peak heart rate, blood pressure and rate pressure, heart rate recovery and daily physical activity. (ClinicalTrials.gov: NCT01887080). RESULTS: At baseline no significant differences were observed between groups. After eight weeks of exercise, the EG significantly increased peak oxygen uptake (p=0.02), test duration (p=0.019), peak rate pressure (p=0.003), peak heart rate (p=0.003) and heart rate recovery (0.025) when compared to the CG. No changes were observed on daily physical activity in both groups. CONCLUSION: This specific phase IV home-based exercise program seems to improve cardiorespiratory fitness, haemodynamics at peak exercise and heart rate recovery, an indicator of cardiac autonomic function.
Assuntos
Aptidão Cardiorrespiratória , Terapia por Exercício , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/reabilitação , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Habitat selection is a complex process, which involves behavioural decisions guided by the multiple needs and constraints faced by individuals. Climate-induced changes in environmental conditions may alter those trade-offs and resulting habitat use patterns. In this study, we investigated the effect of sea temperature on habitat selection and habitat use of acoustically tagged Atlantic cod (Gadus morhua) at the Norwegian Skagerrak coast. Significant relationships between ocean temperature and habitat selection and use were found. Under favourable sea temperature thresholds (<16 °C), cod selected vegetated habitats, such as eelgrass and macroalgae beds, available in shallow areas. Selection for those habitats was especially high at night, when cod tended to ascend to shallower areas, presumably to feed. Selection and use of those habitats decreased significantly as temperature rose. Under increased sea surface temperature conditions, cod were absent from vegetated shallow habitats, both during the day and night, and selected instead non-vegetated rocky bottoms and sand habitats, available in deeper, colder areas. This study shows the dynamic nature of habitat selection and strongly suggests that cod in this region have to trade off food availability against favourable temperature conditions. Future increases in ocean temperature are expected to further influence the spatial behaviour of marine fish, potentially affecting individual fitness and population dynamics.
Assuntos
Ecossistema , Gadus morhua/fisiologia , Temperatura , Animais , Noruega , Oceanos e MaresRESUMO
Paracoccidioides is the agent of paracoccidioidomycosis. Malate synthase plays a crucial role in the pathogenicity and virulence of various fungi, such as those that are human pathogens. Thus, an inhibitor of this enzyme may be used as a powerful antifungal without side effects in patients once these enzymes are absent in humans. Here, we searched for compounds with inhibitory capacity against the malate synthase of Paracoccidioides species (PbMLS). The three-dimensional (3D) structure of PbMLS was determined using the I-TASSER server. Compounds were selected from the ZINC database. Based on the mechanism underlying the interaction of the compounds with PbMLS, it was possible to identify ß-carboline moiety as a standard key structure. The compounds with ß-carboline moiety that are available in our laboratories were investigated. A total of nine alkaloid compounds were selected. The primary mechanisms of interaction of the alkaloid compounds in the binding pocket of PbMLS were identified and compared with the mechanism of interaction of acetyl coenzyme A (acetyl-CoA). We discovered that the amphipathic nature of the compounds, concomitant with the presence of ß-carboline moiety, was crucial for their stability in the binding pocket of PbMLS. In addition, the importance of a critical balance of the polar and nonpolar contacts of the compounds in this region was observed. Four ß-carboline alkaloid compounds showed the ability to inhibit recombinant PbMLS (PbMLSr) activity, Paracoccidioides species growth, and adhesion of the fungus and PbMLSr to the extracellular matrix components. The cytotoxicity of the alkaloids was also evaluated.
Assuntos
Alcaloides/farmacologia , Antifúngicos/farmacologia , Malato Sintase/antagonistas & inibidores , Paracoccidioides/enzimologia , Adesão Celular/efeitos dos fármacosRESUMO
Dengue is the most frequent hemorrhagic viral disease and re-emergent infection in the world. Although thrombocytopenia is characteristically observed in mild and severe forms of dengue, the role of platelet activation in dengue pathogenesis has not been fully elucidated. We hypothesize that platelets have major roles in inflammatory amplification and increased vascular permeability during severe forms of dengue. Here we investigate interleukin (IL)-1ß synthesis, processing, and secretion in platelets during dengue virus (DV) infection and potential contribution of these events to endothelial permeability during infection. We observed increased expression of IL-1ß in platelets and platelet-derived microparticles from patients with dengue or after platelet exposure to DV in vitro. We demonstrated that DV infection leads to assembly of nucleotide-binding domain leucine rich repeat containing protein (NLRP3) inflammasomes, activation of caspase-1, and caspase-1-dependent IL-1ß secretion. Our findings also indicate that platelet-derived IL-1ß is chiefly released in microparticles through mechanisms dependent on mitochondrial reactive oxygen species-triggered NLRP3 inflammasomes. Inflammasome activation and platelet shedding of IL-1ß-rich microparticles correlated with signs of increased vascular permeability. Moreover, microparticles from DV-stimulated platelets induced enhanced permeability in vitro in an IL-1-dependent manner. Our findings provide new evidence that platelets contribute to increased vascular permeability in DV infection by inflammasome-dependent release of IL-1ß.
Assuntos
Plaquetas/metabolismo , Permeabilidade Capilar/fisiologia , Proteínas de Transporte/fisiologia , Dengue/fisiopatologia , Endotélio Vascular/fisiopatologia , Inflamassomos/fisiologia , Interleucina-1beta/metabolismo , Adulto , Plaquetas/efeitos dos fármacos , Plaquetas/ultraestrutura , Caspase 1/fisiologia , Micropartículas Derivadas de Células/metabolismo , Dengue/sangue , Feminino , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Imidazóis/farmacologia , Indóis/farmacologia , Interleucina-1beta/biossíntese , Masculino , Mitocôndrias/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Compostos Organofosforados/farmacologia , Piperidinas/farmacologia , Ativação Plaquetária , Espécies Reativas de Oxigênio/metabolismo , Tosilfenilalanil Clorometil Cetona/análogos & derivados , Tosilfenilalanil Clorometil Cetona/farmacologia , Regulação para Cima/efeitos dos fármacosRESUMO
As part of our continuing chemical and biological analyses of Rubiaceae species from Cerrado, we isolated novel alkaloids 1 and 2, along with known compounds epicatechin, ursolic acid, and oleanolic acid, from Galianthe ramosa. Alkaloid 2 inhibited malate synthase from the pathogenic fungus Paracoccidioides spp. This enzyme is considered an important molecular target because it is not found in humans. Molecular docking simulations were used to describe the interactions between the alkaloids and malate synthase.
Assuntos
Antifúngicos/farmacologia , Carbolinas/farmacologia , Inibidores Enzimáticos/farmacologia , Malato Sintase/antagonistas & inibidores , Paracoccidioides/enzimologia , Alcaloides/química , Alcaloides/farmacologia , Antifúngicos/química , Carbolinas/química , Inibidores Enzimáticos/química , Proteínas Fúngicas/metabolismo , Concentração Inibidora 50 , Malato Sintase/química , Malato Sintase/metabolismo , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Paracoccidioides/efeitos dos fármacos , Paracoccidioides/patogenicidade , Componentes Aéreos da Planta/química , Rubiaceae/químicaRESUMO
INTRODUCTION: In rare instances, pancreatitis can manifest as inguinal edema without typical abdominal symptoms, posing diagnostic challenges. CASE PRESENTATION: We report a case of a man in his 40s, with alcohol addiction, who presented with left inguinal pain and swelling but no other abdominal complaints. Physical examination revealed inguinal tenderness and edema, with no hernia signs. Laboratory results showed leukocytosis and elevated C-reactive protein, inconsistent with the patient's symptoms. Abdominopelvic CT scan revealed peripancreatic fat densification and retroperitoneal fluid extending into the inguinal area. No hernia was evident. Extended analysis revealed elevated amylase and lipase levels, sustaining the diagnosis of pancreatitis. The patient responded well to supportive care and was discharged symptom-free. DISCUSSION: Acute pancreatitis emerging as an inguinoscrotal swelling, in the absence of any abdominal symptoms or signs, is extremely rare and can mimic more common causes of inguinoscrotal swellings, such as incarcerated hernias. This case highlights the ability of leaking pancreatic juice to track widely in the retroperitoneal tissues, particularly on the left side. A high level of suspicion, in combination with a CT scan, is essential for achieving an accurate diagnosis and determining the disease's extent. Failure to diagnose correctly could lead to unnecessary surgical procedures and inappropriate/delayed medical care. CONCLUSION: Inguinal edema as the sole presentation of acute pancreatitis is extremely rare. Therefore, it is essential to maintain a high index of suspicion, especially in patients with a history of alcohol consumption, in order to proceed with prompt treatment and avoid unnecessary surgery.
RESUMO
Introduction: Breast cancer is one of the most common types of cancer affecting women. Despite advancements in early diagnosis, neoadjuvant therapy, and various treatment modalities, mastectomy remains a common procedure for many women. Although some women opt for reconstructive surgery (BR), many do not have the indication, desire, or opportunity to undergo this procedure. Methods: An easily manufactured, washable, lightweight, and inexpensive external breast prosthesis (EBP) model was developed specifically for the study. Participants were presented with five EBP models-one commercially available, three manufactured options, and one created for the study-and were asked to choose a prosthesis. We also evaluated the factors associated with non-adherence to EBP among women who had undergone mastectomy without BR. The chi-square test was used to assess adherence or non-adherence to EBP, while logistic regression was used to identify factors associated with non-adherence. Results: We introduced a low-cost, lightweight, washable EBP model. When participants were asked to choose between two prostheses, the silicone prosthesis was the first choice for 33.9% of the participants, while the prosthesis created for the study emerged as the second choice for 70.5%. Out of the 72 women assessed, 45.8% (33) opted not to use any of the EBP models. Our analysis revealed that age and BMI were significantly associated with non-use of EBP. Conclusion: Multiple barriers contribute to non-adherence to EBP, underscoring the need for interventions aimed at improving patient knowledge and adherence. This study introduces a lightweight, easily reproducible, and low-cost EBP model.