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This work faces the known problem of negative visión among prospective primary teachers regarding science teaching and learning. This is even more acute if gender is taken into account. To overcome this, the use of ethnobotany as a science of proximity is proposed. Specifically, an educational intervention is described that is based on a combination of active methodologies and the use of ethnobotany as a teaching tool for a subject with physics and chemistry contents. Ninety-two university-based primary education trainee teachers participated in the research. By means of questionnaires, information was collected regarding attitudes toward the subject and the use of ethnobotany as a teaching tool, evaluation of the proposal, sustainability awareness, and affective and emotional dimensions. The data indicated a great impact and acceptability. The results show a significant increase in motivation, an improvement in attitudes toward sustainable behavior and a favorable assessment of the proposed didactic tool. This hybrid methodology demonstrates, in the context used, effectiveness in improving the perception of science.
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Microorganisms can play a key role in selenium (Se) bioremediation and the fabrication of Se-based nanomaterials by reducing toxic forms (Se(VI) and Se(IV)) into Se(0). In recent years, omics have become a useful tool in understanding the metabolic pathways involved in the reduction process. This paper aims to elucidate the specific molecular mechanisms involved in Se(VI) reduction by the bacterium Stenotrophomonas bentonitica. Both cytoplasmic and membrane fractions were able to reduce Se(VI) to Se(0) nanoparticles (NPs) with different morphologies (nanospheres and nanorods) and allotropes (amorphous, monoclinic, and trigonal). Proteomic analyses indicated an adaptive response against Se(VI) through the alteration of several metabolic pathways including those related to energy acquisition, synthesis of proteins and nucleic acids, and transport systems. Whilst the thioredoxin system and the Painter reactions were identified to play a crucial role in Se reduction, flagellin may also be involved in the allotropic transformation of Se. These findings suggest a multi-modal reduction mechanism is involved, providing new insights for developing novel strategies in bioremediation and nanoparticle synthesis for the recovery of critical materials within the concept of circular economy.
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The search for new agents targeting different forms of cell death is an important research focus for developing new and potent antitumor therapies. As a contribution to this endeavor, we have designed and synthesized a series of new substituted 3,4-dihydro-2H-1,4-benzoxazine derivatives. These compounds have been evaluated for their efficacy against MCF-7 breast cancer and HCT-116 colon cancer cell lines. Overall, substituting this heterocycle led to improved antiproliferative activity compared to the unsubstituted derivative 1. The most active compounds, 2b and 4b, showed IC50 values of 2.27 and 3.26 µM against MCF-7 cells and 4.44 and 7.63 µM against HCT-116 cells, respectively. To investigate the mechanism of action of the target compounds, the inhibition profile of 8 kinases involved in cell signaling was studied highlighting residual activity on HER2 and JNK1 kinases. 2b and 4b showed a consistent binding mode to both receptor kinases, establishing significant interactions with known and catalytically important domains and residues. Compounds 2b and 4b exhibit potent cytotoxic activity by disrupting cell membrane permeability, likely triggering both inflammatory and non-inflammatory cell death mechanisms. This dual capability increases their versatility in the treatment of different stages or types of tumors, providing greater flexibility in clinical applications.
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Antineoplásicos , Benzoxazinas , Permeabilidade da Membrana Celular , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Benzoxazinas/química , Benzoxazinas/farmacologia , Benzoxazinas/síntese química , Relação Estrutura-Atividade , Permeabilidade da Membrana Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Estrutura Molecular , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Relação Dose-Resposta a Droga , Células HCT116 , Células MCF-7RESUMO
OBJECTIVES: Identifying host response biomarkers implicated in the emergence of organ failure during infection is key to improving the early detection of this complication. METHODS: Twenty biomarkers of innate immunity, T-cell response, endothelial dysfunction, coagulation, and immunosuppression were profiled in 180 surgical patients with infections of diverse severity (IDS) and 53 with no infection (nIDS). Those better differentiating IDS/nIDS in the area under the curve were combined to test their association with the sequential organ failure assessment score by linear regression analysis in IDS. Results were validated in another IDS cohort of 174 patients. RESULTS: C-reactive protein, procalcitonin, pentraxin-3, lipocalin-2 (LCN2), tumoral necrosis factor-α, angiopoietin-2, triggering receptor expressed on myeloid cells-1 (TREM-1) and interleukin (IL)-15 yielded an area under the curve ≥0.75 to differentiate IDS from nIDS. The combination of LCN2, IL-15, TREM-1, angiopoietin-2 (Dys-4) showed the strongest association with sequential organ failure assessment score in IDS (adjusted regression coefficient; standard error; P): Dys-4 (3.55;0.44; <0.001), LCN2 (2.24; 0.28; <0.001), angiopoietin-2 (1.92; 0.33; <0.001), IL-15 (1.78; 0.40; <0.001), TREM-1(1.74; 0.46; <0.001), tumoral necrosis factor-α (1.60; 0.31; <0.001), pentraxin-3 (1.12; 0.18; <0.001), procalcitonin (0.85; 0.12; <0.001). Dys-4 provided similar results in the validation cohort. CONCLUSIONS: There is a synergistic impact of innate immunity hyper-activation (LCN2, IL-15, TREM-1) and endothelial dysfunction (angiopoietin-2) on the magnitude of organ failure during infection.
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Angiopoietina-2 , Biomarcadores , Proteína C-Reativa , Imunidade Inata , Insuficiência de Múltiplos Órgãos , Sepse , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/sangue , Insuficiência de Múltiplos Órgãos/imunologia , Sepse/imunologia , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Angiopoietina-2/sangue , Idoso , Receptor Gatilho 1 Expresso em Células Mieloides , Componente Amiloide P Sérico/metabolismo , Pró-Calcitonina/sangue , Lipocalina-2/sangue , Interleucina-15/sangue , Fator de Necrose Tumoral alfa/sangue , AdultoRESUMO
Bioprospecting the secondary metabolism of underexplored Actinomycetota taxa is a prolific route to uncover novel chemistry. In this work, we report the isolation, structure elucidation, and bioactivity screening of cellulamides A and B (1 and 2), two novel linear peptides obtained from the culture of the macroalga-associated Cellulosimicrobium funkei CT-R177. The host of this microorganism, the Chlorophyta Codium tomentosum, was collected in the northern Portuguese coast and, in the scope of a bioprospecting study focused on its associated actinobacterial community, strain CT-R177 was isolated, taxonomically identified, and screened for the production of antimicrobial and anticancer compounds. Dereplication of a crude extract of this strain using LC-HRMS(/MS) analysis unveiled a putative novel natural product, cellulamide A (1), that was isolated following mass spectrometry-guided fractionation. An additional analog, cellulamide B (2) was obtained during the chromatographic process and chemically characterized. The chemical structures of the novel linear peptides, including their absolute configurations, were elucidated using a combination of HRMS, 1D/2D NMR spectroscopy, and Marfey's analysis. Cellulamide A (1) was subjected to a set of bioactivity screenings, but no significant biological activity was observed. The cellulamides represent the first family of natural products reported from the Actinomycetota genus Cellulosimicrobium, showcasing not only the potential of less-explored taxa but also of host-associated marine strains for novel chemistry discovery.
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Peptídeos , Humanos , Peptídeos/química , Peptídeos/farmacologia , Peptídeos/isolamento & purificação , Actinobacteria/química , Actinobacteria/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Organismos Aquáticos , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Linhagem Celular Tumoral , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificaçãoRESUMO
INTRODUCTION: The main objective of this study was to estimate survival and changes in lung function in patients with chronic hypersensitivity pneumonitis (HP), both fibrotic (f-HP) and nonfibrotic (nf-HP), and to compare them with those in patients with idiopathic pulmonary fibrosis (IPF). METHODS: HP was diagnosed based on antigen exposure, HRCT (high-resolution CT scan), BAL (bronchoalveolar lavage), and histology. According to HRCT, HP was classified into fibrotic and non-fibrotic phenotypes. In most cases, IPF was diagnosed based on HRCT findings. RESULTS: We identified 84 patients: 46 with IPF, 18 with f-HP, and 20 with nf-HP. Five-year survival was 23.9% in IPF, 72% in f-HP, and 100% in nf-HP (p <0.0001). Honeycombing was associated with decreased survival in IPF (p <0.001) and in f-HP (p <0.0001). The mean loss of FVC (forced vital capacity) % pred. (percent predicted) was -18.3% in IPF (p =0.001), -4.8% in f-HP, and -6.0% in nf-HP. The mean change in DLCO (diffusion capacity for carbon monoxide) % pred. was -10.2% in IPF (p <0.002), -0.5% in f-HP, and +1.9% in nf-HP. The agreement between radiological phenotypes and histology in HP was 89.6%. CONCLUSIONS: We found shorter survival in IPF, followed by f-HP, and nf-HP. Over time, we did not find significant changes in FVC% pred. or DLCO% pred. in HP, while a significant decline in IPF was noted. In HP, we found strong agreement between radiological phenotypes and histology. Radiological signs suggestive of lung fibrosis in HP were reliable for the diagnosis of f-HP and seem to have intrinsic prognostic value.
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BACKGROUND: Despite the improvement in therapies, pancreatic cancer represents one of the most cancer-related deaths. In our hypothesis, we propose that Hyperthermic Intraperitoneal Chemotherapy with gemcitabine after pancreatic cytoreductive surgery could reduce tumor progression by reducing residual neoplastic volume and residual pancreatic cancer stem cells. MATERIALS AND METHODS: A randomized trial involving 42 patients. All patients were diagnosed with pancreatic ductal adenocarcinoma. Group I: R0 resection. Group II. R0 resection and HIPEC with gemcitabine (120 mg/m2 for 30 min). Effectiveness was measured with analysis of overall survival, disease-free survival, distant recurrence, locoregional recurrence, and measuring of pancreatic cancer stem cells (EpCAM+CXCR4+CD133+). RESULTS: From 2017 to 2023, 63 patients were recruited for our clinical trial; 21 patients were included in each group, and 21 were excluded. Locoregional recurrence, p-value: 0.022, was lower in the experimental group. There were no significant differences between the two groups in hospital mortality, perioperative complications, or hospital costs. We found a significant decrease in pancreatic cancer stem cells in patients in the experimental group after treatment, p -value of 0.018. CONCLUSIONS: The use of HIPEC with gemcitabine after surgery in patients with resectable pancreatic ductal adenocarcinoma reduces locoregional recurrence and may be associated with a significant decrease in pancreatic cancer stem cells.
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BACKGROUND: To date, there are no tools for the nursing staff to gain systematic insight on the experience lived by patients with chronic heart failure. The objective of this study was to develop a scale for this purpose. METHODS: The study was conducted between January 2018 and December 2020 in three Spanish hospitals. The process described by DeVellis was used for the development of the scale. The items were built based on a phenomenological study and a systematic review of the literature. Next, feedback from a panel of experts was obtained, the scale was administered to a sample of patients with chronic heart failure, and a cognitive interview and an observational study were conducted to create the final version of the scale. RESULTS: The first version of the scale had in seven domains and 76 items. After its evaluation by a panel of experts, it was reduced to a second version with six domains and 55 items. Following the administration of Version 2 to 17 patients (58.8% male, mean age 59.53, 70.6% classified as NYHA functional class II), five items were modified and two eliminated. Thus, the third version of the UNAV-CHF Experience Scale was composed of six domains and 53 items. CONCLUSIONS: This study presents the development of the UNAV-experience of living with chronic heart failure scale. It is an original and novel instrument that allows systematically explore this experience. A larger-scale study is necessary to confirm the validity of our scale.
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Insuficiência Cardíaca , Insuficiência Cardíaca/psicologia , Humanos , Masculino , Feminino , Doença Crônica , Pessoa de Meia-Idade , Idoso , Espanha , Inquéritos e Questionários , Qualidade de VidaRESUMO
Background: The ability to predict a long duration of mechanical ventilation (MV) by clinicians is very limited. We assessed the value of machine learning (ML) for early prediction of the duration of MV > 14 days in patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Methods: This is a development, testing, and external validation study using data from 1173 patients on MV ≥ 3 days with moderate-to-severe ARDS. We first developed and tested prediction models in 920 ARDS patients using relevant features captured at the time of moderate/severe ARDS diagnosis, at 24 h and 72 h after diagnosis with logistic regression, and Multilayer Perceptron, Support Vector Machine, and Random Forest ML techniques. For external validation, we used an independent cohort of 253 patients on MV ≥ 3 days with moderate/severe ARDS. Results: A total of 441 patients (48%) from the derivation cohort (n = 920) and 100 patients (40%) from the validation cohort (n = 253) were mechanically ventilated for >14 days [median 14 days (IQR 8-25) vs. 13 days (IQR 7-21), respectively]. The best early prediction model was obtained with data collected at 72 h after moderate/severe ARDS diagnosis. Multilayer Perceptron risk modeling identified major prognostic factors for the duration of MV > 14 days, including PaO2/FiO2, PaCO2, pH, and positive end-expiratory pressure. Predictions of the duration of MV > 14 days showed modest discrimination [AUC 0.71 (95%CI 0.65-0.76)]. Conclusions: Prolonged MV duration in moderate/severe ARDS patients remains difficult to predict early even with ML techniques such as Multilayer Perceptron and using data at 72 h of diagnosis. More research is needed to identify markers for predicting the length of MV. This study was registered on 14 August 2023 at ClinicalTrials.gov (NCT NCT05993377).
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Introduction: The aim of the study is to address embodied planning in climbing. Embodied planning was conceptualized as the interaction between perceptual-cognitive pre-planning and motor execution. Methods: In an experimental study, 18 climbers were asked to pre-plan a climbing route and to perform the route afterward. During pre-planning, the visual search pattern of climbers was captured using a portable eye tracker. After previewing, they were invited to climb the wall. Results: Results revealed that holds looked at during pre-planning were used twice as much during route execution than those not looked at. The duration of fixations was longer for holds used than those not used during route execution. The experience of climbers (training years) correlated with visual strategies and climbing performance, such that experienced participants climbed faster and fixated at the holds not used for a shorter time. Discussion: The visual behaviors of climbers were influenced by their past sensorimotor experiences during route previewing, impacting subsequent climbing performance.
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Piperazic acid is a cyclic nonproteinogenic amino acid that contains a hydrazine N-N bond formed by a piperazate synthase (KtzT-like). This amino acid, found in bioactive natural products synthesized by non-ribosomal peptide synthetases (NRPSs), confers conformational constraint to peptides, an important feature for their biological activities. Genome mining of Streptomyces strains has been revealed as a strategy to identify biosynthetic gene clusters (BGCs) for potentially active compounds. Moreover, the isolation of new strains from underexplored habitats or associated with other organisms has allowed to uncover new BGCs for unknown compounds. The in-house "Carlos Sialer (CS)" strain collection consists of seventy-one Streptomyces strains isolated from the cuticle of leaf-cutting ants of the tribe Attini. Genomes from twelve of these strains have been sequenced and mined using bioinformatics tools, highlighting their potential to encode secondary metabolites. In this work, we have screened in silico those genomes, using KtzT as a hook to identify BGCs encoding piperazic acid-containing compounds. This resulted in uncovering the new BGC dpn in Streptomyces sp. CS113, which encodes the biosynthesis of the hybrid polyketide-depsipeptide diperamycin. Analysis of the diperamycin polyketide synthase (PKS) and NRPS reveals their functional similarity to those from the aurantimycin A biosynthetic pathway. Experimental proof linking the dpn BGC to its encoded compound was achieved by determining the growth conditions for the expression of the cluster and by inactivating the NRPS encoding gene dpnS2 and the piperazate synthase gene dpnZ. The identity of diperamycin was confirmed by High-Resolution Mass Spectrometry (HRMS) and Nuclear Magnetic Resonance (NMR) and by analysis of the domain composition of modules from the DpnP PKS and DpnS NRPS. The identification of the dpn BGC expands the number of BGCs that have been confirmed to encode the relatively scarcely represented BGCs for depsipeptides of the azinothricin family of compounds and will facilitate the generation of new-to-nature analogues by combinatorial biosynthesis.
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Depsipeptídeos , Piridazinas , Streptomyces , Streptomyces/genética , Streptomyces/metabolismo , Peptídeos Catiônicos Antimicrobianos/metabolismo , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Família Multigênica , Depsipeptídeos/genética , Depsipeptídeos/metabolismo , Aminoácidos/metabolismoRESUMO
Multidisciplinary strategies have transformed the management of advanced ovarian cancer. We aimed to evaluate the effectiveness of paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical cytoreduction for ovarian peritoneal metastases in a randomized phase III trial conducted between August 2012 and December 2019. Seventy-six patients were randomized to either the HIPEC or no HIPEC group. Although median values for the primary endpoints (recurrence-free survival (RFS) and overall survival (OS)) revealed superior outcomes for the HIPEC (RFS: 23 months, OS: 48 months) over the control group (RFS: 19 months, OS: 46 months), these differences were not statistically significant (p = 0.22 and p = 0.579). Notably, the HIPEC group demonstrated significantly higher 5-year OS and 3-year RFS rates (47.2% and 47.5%) compared to patients without HIPEC (34.5% and 21.3%). Stratification according to Peritoneal Surface Disease Severity Score (PSDSS) showed improved OS and RFS for patients with lower PSDSS (I-II) in the HIPEC-treated group (p = 0.033 and p = 0.042, respectively). The Clavien-Dindo classification of adverse event grades revealed no significant differences between HIPEC and controls (p = 0.482). While overall results were not statistically significant, our long-term follow-up emphasized the potential benefit of HIPEC-associated cytoreduction with paclitaxel, particularly in selected ovarian cancer patients with lower PSDSS indices.
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Hipertermia Induzida , Neoplasias Ovarianas , Neoplasias Peritoneais , Feminino , Humanos , Paclitaxel/uso terapêutico , Quimioterapia Intraperitoneal Hipertérmica , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Seguimentos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgiaRESUMO
OBJECTIVES: Identifying patients with COVID-19 who are at risk of poor evolution is key to early decide on their hospitalization. We evaluated the combined impact of nucleocapsid (N)-antigenemia profiled by a rapid test and antibodies against the S1 subunit of the SARS-CoV S protein (S1) on the hospitalization risk of patients with COVID-19. METHODS: N-antigenemia and anti-S1 antibodies were profiled at admission to the emergency department in 146 patients with COVID-19 using the Panbio® antigen Rapid Test and the SARS-CoV-2 immunoglobulin G II Quant/SARS-CoV-2 immunoglobulin G assay from Abbott. A multivariable analysis was used to evaluate the impact of these factors on hospitalization. RESULTS: Patients with a positive N-antigen test in plasma and anti-S1 levels <2821 arbitrary units/mL needed hospitalization more frequently (20 of 23, 87%). A total of 20 of 71 (28.2%) of those showing a negative N-antigen test and anti-S1 ≥2821 arbitrary units/mL were hospitalized for 18 of 52 (34.6%) of the patients with only one of these conditions. Patients with a positive N-antigen test and low antibody levels showed an odds ratio, 95% confidence interval, and P-value for hospitalization of 18.21, 2.74-121.18, and 0.003, respectively, and exhibited the highest mortality (30.4%). CONCLUSIONS: Simultaneous profiling of a rapid N-antigen test in plasma and anti-S1 levels could help to early identify patients with COVID-19 needing hospitalization.
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COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Anticorpos Antivirais , Imunoglobulina G , HospitalizaçãoRESUMO
Genome analysis of strain Streptomyces sp. CA-278952 revealed a biosynthetic gene cluster encoding a putative lipopeptide with a sequence containing an Asp-Gly-Glu-Ala motif. We envisioned that this motif could mimic the canonical Asp-X-Asp-Gly sequence found in previously reported calcium-dependent lipopeptide antibiotics. Chemical investigation of the producing strain led to the discovery of three novel lipodepsipeptides, dilarmycins A-C. The calcium-dependent antibacterial activity of the new compounds was confirmed against the Gram-positive pathogens methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus.
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Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Antibacterianos/química , Cálcio , Lipopeptídeos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Malignant melanoma (MM) is a highly aggressive form of skin cancer whose incidence continues to rise worldwide. If diagnosed at an early stage, it has an excellent prognosis, but mortality increases significantly at advanced stages after distant spread. Unfortunately, early detection of aggressive melanoma remains a challenge. OBJECTIVES: To identify novel blood-circulating biomarkers that may be useful in the diagnosis of MM to guide patient counselling and appropriate disease management. METHODS: In this study, 105 serum samples from 26 healthy patients and 79 with MM were analysed using an untargeted approach by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to compare the metabolomic profiles of both conditions. Resulting data were subjected to both univariate and multivariate statistical analysis to select robust biomarkers. The classification model obtained from this analysis was further validated with an independent cohort of 12 patients with stage I MM. RESULTS: We successfully identified several lipidic metabolites differentially expressed in patients with stage I MM vs. healthy controls. Three of these metabolites were used to develop a classification model, which exhibited exceptional precision (0.92) and accuracy (0.94) when validated on an independent sample. CONCLUSIONS: These results demonstrate that metabolomics using LC-HRMS is a powerful tool to identify and quantify metabolites in bodily fluids that could serve as potential early diagnostic markers for MM.
Melanoma is a type of skin cancer that can be deadly if it is not detected at an early stage. Unfortunately, the early detection of melanoma is challenging. Our team has developed a model that could be used to predict whether a person has stage I malignant melanoma based on blood serum analysis. The model was trained on data from a group of people with melanoma and it was found to be accurate in predicting melanoma at an early stage. This means that the model could be used to identify people who have skin cancer before it progresses and becomes more complicated to treat. Although the researchers recommend that further studies are conducted to validate the model in a larger population of people, this research could help with the early diagnosis of melanoma and work toward improving survival rates.
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Melanoma , Neoplasias Cutâneas , Humanos , Projetos Piloto , Detecção Precoce de Câncer , Metabolômica , Biomarcadores , Espectrometria de Massa com Cromatografia LíquidaRESUMO
BACKGROUND: Polycythemia vera (PV) patients are classified as high or low thrombotic risk based on age and prior history of thrombosis. Despite adherence to treatment recommendations, vascular events remain frequent, leading us to question whether thrombotic risk stratification could be improved. We previously reported an association between thrombotic events and mutations in DTA genes (DNMT3A, TET2, and ASXL1). The objective of this study was to confirm this observation in a larger series of PV patients. METHODS: PV patients with a minimum follow-up of 3 years were recruited from 8 European centers. Medical history was searched for thrombotic event recorded at any time and next-generation sequencing carried out with a myeloid panel. Multivariable logistic regression evaluated the impact of variables on thrombotic risk. Kaplan-Meier thrombosis-free survival curves were compared by the log rank test. Associations in the total cohort were confirmed in a case-control study to exclude selection bias. RESULTS: Of the 136 patients recruited, 74 (56.1%) had a thrombotic event, with an incidence density of 2.83/100 person-years. In multivariable analysis, DTA mutation was a risk factor for thrombotic event, being predictive for shorter thrombosis-free survival in the whole cohort (p = 0.007), as well as in low-risk patients (p = 0.039) and older patients (p = 0.009), but not for patients with a prediagnostic event. A gender- and age-matched case-control study confirmed the increased risk of thrombotic event for PV patients with a DTA mutation. CONCLUSION: Our results support the use of molecular testing at diagnosis to help predict which PV patients are at higher risk of developing thrombosis.
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DNA (Citosina-5-)-Metiltransferases , DNA Metiltransferase 3A , Proteínas de Ligação a DNA , Dioxigenases , Mutação , Policitemia Vera , Proteínas Proto-Oncogênicas , Proteínas Repressoras , Trombose , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Trombose/genética , Fatores de Risco , Idoso , Policitemia Vera/genética , Policitemia Vera/complicações , Proteínas Repressoras/genética , Fatores Etários , Proteínas Proto-Oncogênicas/genética , DNA (Citosina-5-)-Metiltransferases/genética , Proteínas de Ligação a DNA/genética , Estudos de Casos e Controles , Adulto , Europa (Continente)/epidemiologia , Incidência , Predisposição Genética para Doença , Medição de Risco , Estimativa de Kaplan-Meier , Idoso de 80 Anos ou maisRESUMO
The increase in global travel and the incorrect and excessive use of antibiotics has led to an unprecedented rise in antibiotic resistance in bacterial and fungal populations. To overcome these problems, novel bioactive natural products must be discovered, which may be found in underexplored environments, such as estuarine habitats. In the present work, estuarine actinomycetotal strains were isolated with conventional and iChip techniques from the Tagus estuary in Alcochete, Portugal, and analysed for different antimicrobial bioactivities. Extracts were produced from the isolated cultures and tested for bioactivity against Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Aspergillus fumigatus ATCC 240305, Candida albicans ATCC 10231 and Trichophyton rubrum FF5. Furthermore, bioactive extracts were subjected to dereplication by high-performance liquid chromatography (HPLC) and high-resolution mass spectrometry (HRMS) to putatively identify their chemical components. In total, 105 isolates belonging to 3 genera were obtained. One which was isolated, MTZ3.1 T, represents a described novel taxon for which the name Streptomyces meridianus was proposed. Regarding the bioactivity testing, extracts from 12 strains proved to be active against S. aureus, 2 against E. coli, 4 against A. fumigatus, 3 against C. albicans and 10 against T. rubrum. Dereplication of bioactive extracts showed the presence of 28 known bioactive molecules, 35 hits have one or more possible matches in the DNP and 18 undescribed ones. These results showed that the isolated bacteria might be the source of new bioactive natural products.
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An appealing strategy for finding novel bioactive molecules in Nature consists in exploring underrepresented and -studied microorganisms. Here, we investigated the antimicrobial and tumoral anti-proliferative bioactivities of twenty-three marine and estuarine bacteria of the fascinating phylum Planctomycetota. This was achieved through extraction of compounds produced by the Planctomycetota cultured in oligotrophic medium followed by an antimicrobial screening against ten relevant human pathogens including Gram-positive and Gram-negative bacteria, and fungi. Cytotoxic effects of the extracts were also evaluated against five tumoral cell lines. Moderate to potent activities were obtained against Enterococcus faecalis, methicillin-sensitive and methicillin-resistant Staphylococcus aureus and vancomycin-sensitive and vancomycin-resistant Enterococcus faecium. Anti-fungal effects were observed against Trichophyton rubrum, Candida albicans and Aspergillus fumigatus. The highest cytotoxic effects were observed against human breast, pancreas and melanoma tumoral cell lines. Novipirellula caenicola and Rhodopirellula spp. strains displayed the widest spectrum of bioactivities while Rubinisphaera margarita ICM_H10T affected all Gram-positive bacteria tested. LC-HRMS analysis of the extracts did not reveal the presence of any known bioactive natural product, suggesting that the observed activities are most likely caused by novel molecules, that need identification. In summary, we expanded the scope of planctomycetal species investigated for bioactivities and demonstrated that various strains are promising sources of novel bioactive compounds, which reenforces the potential biotechnological prospects offered by Planctomycetota.