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1.
Fish Shellfish Immunol ; 153: 109835, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39147180

RESUMO

Galectin-4 belongs to the galactoside-binding protein family and is a type of tandem repeat galectin. Despite previous studies indicating its importance in fish immunology, a comprehensive investigation is necessary to fully understand its role in immunomodulatory functions and cellular dynamics. Therefore, this study aimed to explore the immunomodulatory functions of galectin-4 with a particular focus on its antimicrobial and cellular proliferative properties. The open reading frame of PhGal4 spans 1092 base pairs and encodes a soluble protein of 363 amino acids with a theoretical isoelectric point (IEP) of 6.39 and a molecular weight of 39.411 kDa. Spatial expression analysis under normal physiological conditions revealed ubiquitous expression of PhGal4 across all examined tissues, with the highest level observed in intestinal tissue. Upon stimulation with poly I:C, LPS, and L. garvieae, a significant increase (p < 0.05) in PhGal4 expression was observed in both blood and spleen tissues. Subsequent subcellular localization assay demonstrated that PhGal4 was predominantly localized in the cytoplasm. The recombinant PhGal4 (rPhGal4) exhibited specific binding capabilities to pathogen-associated molecular patterns (PAMPs), including LPS and peptidoglycan, but not poly I:C. The rPhGal4 negatively affected the bacterial growth kinetics. Additionally, rPhGal4 demonstrated complete hemagglutination of fish erythrocytes, which could be inhibited by the presence of D-galactose and α-lactose. The overexpression of PhGal4 in FHM epithelial cells demonstrated a significant suppression of viral replication during VHSV infection. Furthermore, the in vitro scratch assay and WST-1 assay demonstrated a wound healing effect of PhGal4 overexpression in FHM cells, potentially achieved through the promotion of cell proliferation by activating genes involved in cell cycle regulation. In conclusion, the responsive expression to immune stimuli, antimicrobial properties, and cell proliferation promotion of PhGal4 suggest that it plays a crucial role in immunomodulation and cellular dynamics of red-lip mullet. The findings in this study shed light on the multifunctional nature of galectin-4 in teleost fish.


Assuntos
Proliferação de Células , Proteínas de Peixes , Galectina 4 , Smegmamorpha , Animais , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/química , Proliferação de Células/efeitos dos fármacos , Galectina 4/genética , Galectina 4/imunologia , Galectina 4/química , Smegmamorpha/imunologia , Smegmamorpha/genética , Imunidade Inata/genética , Filogenia , Sequência de Aminoácidos , Perfilação da Expressão Gênica/veterinária , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Poli I-C/farmacologia , Alinhamento de Sequência/veterinária , Lipopolissacarídeos/farmacologia
2.
Fish Shellfish Immunol ; 153: 109859, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39182708

RESUMO

Interferon-related developmental regulator 1 (IFRD1) is a viral responsive gene associated with interferon-gamma. Herein, we identified the IFRD1 gene (EaIFRD1) from red-spotted grouper (Epinephelus akaara), evaluated its transcriptional responses, and investigated its functional features using various biological assays. EaIFRD1 encodes a protein comprising 428 amino acids with a molecular mass of 48.22 kDa. It features a substantial domain belonging to the interferon-related developmental regulator superfamily. Spatial mRNA expression of EaIFRD1 demonstrated the highest expression levels in the brain and the lowest in the skin. Furthermore, EaIFRD1 mRNA expression in grouper tissues exhibited significant modulation in response to immune stimulants, including poly (I:C), LPS, and nervous necrosis virus (NNV) infection. We analyzed downstream gene regulation by examining type Ⅰ interferon pathway genes following EaIFRD1 overexpression. The results demonstrated a significant upregulation in cells overexpressing EaIFRD1 compared to the control after infection with viral hemorrhagic septicemia virus (VHSV). A subcellular localization assay confirmed the nuclear location of the EaIFRD1 protein, consistent with its role as a transcriptional coactivator. Cells overexpressing EaIFRD1 exhibited increased migratory activity, enhancing wound-healing capabilities compared to the control. Additionally, under H2O2 exposure, EaIFRD1 overexpression protected cells against oxidative stress. Overexpression of EaIFRD1 also reduced poly (I:C)-mediated NO production in RAW267.4 macrophage cells. In FHM cells, EaIFRD1 overexpression significantly reduced VHSV virion replication. Collectively, these findings suggest that EaIFRD1 plays a crucial role in the antiviral immune response and immunological regulation in E. akaara.


Assuntos
Bass , Doenças dos Peixes , Proteínas de Peixes , Imunidade Inata , Animais , Sequência de Aminoácidos , Bass/imunologia , Bass/genética , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Lipopolissacarídeos/farmacologia , Nodaviridae/fisiologia , Novirhabdovirus/fisiologia , Filogenia , Poli I-C/farmacologia , Infecções por Vírus de RNA/imunologia , Infecções por Vírus de RNA/veterinária , Alinhamento de Sequência/veterinária
3.
Fish Shellfish Immunol ; 154: 109939, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39366647

RESUMO

Thioredoxin domain-containing protein 12 (TXNDC12) is a member of the thioredoxin-like superfamily that contributes to various thiol-dependent metabolic activities in all living organisms. In this research, the TXNDC12 gene from yellowtail clownfish (Amphiprion clarkii) was structurally characterized using in silico tools, assessed for immunological expression, and evaluated for biological activity using recombinant protein and cellular overexpression. The deduced coding sequence of AcTXNDC12 comprised a 522-bp nucleotide, encoding 173 amino acids with a predicted molecular mass of 19.198 kDa. The AcTXNDC12 protein consists of a66WCGAC70 active motif and a170GDEL173 signature. The highest tissue-specific expression of AcTXNDC12 was observed in the brain tissue, with significant modulation observed in the blood and gill tissues following stimulation of polyinosinic: polycytidylic acid, lipopolysaccharides (LPS), and Vibrio harveyi. In functional assays, recombinant AcTXNDC12 protein (rAcTXNDC12) showed insulin disulfide reduction activity, 2,2'-azino-di-(3-ethylbenzthiazoline sulfonic acid) decolorization antioxidant capacity, and ferric (Fe3+) reducing antioxidant potential. Additionally, a significant reduction in nitric oxide production was observed in AcTXNDC12-overexpressed RAW 264.7 cells upon LPS stimulation. Furthermore, genes associated with the regulation of oxidative stress, including nuclear factor erythroid 2-related factor 2 (Nrf2), catalase (Cat), peroxiredoxin 1 (Prx1), and ribonucleotide reductase catalytic subunit M1 (Rrm1) were significantly upregulated in fathead minnow cells overexpressing AcTXNDC12 in response to H2O2 treatment. The scratch wound healing assay demonstrated tissue regeneration and cell proliferation ability upon AcTXNDC12 overexpression. Altogether, the current study elucidated the antioxidant activity, immunological importance, and wound-healing effect of the AcTXNDC12 gene in yellowtail clownfish, providing valuable insights for advancing the aquaculture of A. clarkii fish.

4.
Nanotechnology ; 35(23)2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38422541

RESUMO

Structural and electrochemical properties of bismuth ferrite nanostructures produced by pulsed laser deposition with various morphologies are reported. The nanostructures are also explored as electrode materials for high-performance supercapacitors. Scanning electron microscopy images revealed that various bismuth ferrite morphologies were produced by varying the background pressure (10-6, 0.01, 0.10, 0.25, 0.50, 1.0, 2.0 and 4.0 Torr) in the deposition chamber and submitting them to a thermal treatment after deposition at 500◦C. The as-deposited bismuth ferrite nanostructures range from very compact thin-film (10-6, 0.01, 0.10 Torr), to clustered nanoparticles (0.25, 0.50, 1.0 Torr), to very dispersed arrangement of nanoparticles (2.0 and 4.0 Torr). The electrochemical characteristic of the electrodes was investigated through cyclic voltammetry process. The increase in the specific surface area of the nanostructures as background pressure in the chamber increases does not lead to an increase in interfacial capacitance. This is likely due to the wakening of electrical contact between nanoparticles with increasing porosity of the nanostructures. The thermal treatment increased the contact between nanoparticles, which caused an increase in the interfacial capacitance of the nanostructure deposited under high background pressure in the chamber.

5.
Oral Dis ; 30(7): 4721-4730, 2024 10.
Artigo em Inglês | MEDLINE | ID: mdl-38438326

RESUMO

OBJECTIVE: This observational study aimed to explore the metagenomics of subgingival biofilms in individuals with varying degrees of asthma, from severe to none, to elucidate the association between the subgingival microbiome and asthma. MATERIALS AND METHODS: Subgingival biofilm samples were collected from thirty participants at the Asthma Control Program Outpatient Clinic in Bahia (ProAR). These samples were categorized into six groups based on the severity of asthma and the presence or absence of periodontitis. We employed next-generation sequencing (Illumina MiSeq), targeting the 16S rRNA gene, to characterize the microbial communities present. Our analysis included descriptive statistics and sequencing data, evaluated using multivariate statistical methods such as the Shannon index, principal coordinate analysis, and the Bray-Curtis dissimilarity. RESULTS: Our findings indicate a higher prevalence of periodontally detrimental bacterial genera in individuals with severe asthma and periodontitis. Additionally, individuals with asthma, but without periodontitis, exhibited a tendency toward dysbiosis, particularly in cases of severe asthma. CONCLUSION: This research provides new insights into the composition of the subgingival microbiome in individuals with varying severities of asthma and periodontitis. The genera identified in this study underscore the need for further investigations to build upon these findings.


Assuntos
Asma , Biofilmes , Microbiota , Periodontite , Humanos , Asma/microbiologia , Periodontite/microbiologia , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Metagenômica/métodos , RNA Ribossômico 16S/análise , Gengiva/microbiologia , Disbiose/microbiologia , Adulto Jovem
6.
J Anim Breed Genet ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39291375

RESUMO

This study aimed to estimate variance components (VCs) for growth and reproductive traits in Nellore cattle using two relationship matrices (pedigree relationship A matrix and pedigree plus genomic relationship H matrix), and records collected before and after genomic selection (GS) implementation. The study also evaluated how genomic breeding values (GEBV) are affected by variance components and discarding old records. The analysed traits were weight at 120 days (W120), weight and scrotal circumference at 450 days (W450 and SC450, respectively). Three datasets were used to estimate VCs, including all phenotypic information (All) or records for animals born before or after GS implementation (Before or After datasets, respectively). Both relationship matrices were considered for VC estimation, the A matrix was used in all three datasets and VC from each combination were named as A_Before, A_After, and A_All). The H was used in two datasets: H_All and H_After. Different VCs were used for GEBV prediction through ssGBLUP. This step used two possible Datasets, using all available phenotypic data (Dataset 1) or just records collected since GS implementation (Dataset 2). Validation was conducted using accuracy, bias and dispersion according to the LR method and prediction accuracy from corrected phenotypes. The heritability of all traits increased from A_Before to A_After, while estimates for A_All were intermediary. In the previous order, the estimates were 0.16, 0.17, and 0.15 for W120; 0.31, 0.39, and 0.35 for W450; 0.35, 0.47, and 0.41 for SC. For W450 and SC, using the H matrix reduced the heritability (0.33 and 0.32 for W450; 0.41 and 0.38 for SC for H_After and H_All, respectively). For W120, Dataset1 and VCs from A_After showed the highest accuracy for direct and maternal GEBV (0.953 and 0.868). For W450, Dataset 1 and VC from H_After allowed the highest accuracy (0.854) but use Dataset 2 and same VC source yield similar value (0.846). For SC, Dataset 2 with VC from H_After showed the highest accuracy (0.925). To use Dataset 2 does not cause important changes in bias or dispersion with respect to Dataset 1. The VC and genetic parameters changed for W120, W450, and SC450, using records before or after the GS implementation. For W450 and SC450, genetic variance and heritability estimates increased with the use of GS. For W120, genomic predictions were more accurate using A for VC estimation. Accuracy gains were observed for W450 and SC450 using H in VC estimation and/or discarding records before GS. It is possible to discard phenotypic records before GS implementation without generating bias or dispersion in the GEBV of young candidates.

7.
Molecules ; 29(18)2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39339420

RESUMO

Microplastics (MPs) contribute to the overall pollution of water sources, affecting not only aquatic ecosystems but also water for human consumption (WHC). Currently, there needs to be a global consensus on safe levels of microplastics in WHC, which will allow regulatory efforts and risk assessments to be carried out. Therefore, this study aims to characterize MP particles in WHC of the Lisbon water supply system (LWSS) and compare two approaches to quantify these particles (length and width of the particles, and the area equivalent diameter (AED) of the particles). The quantification of MP particles was made via micro-FTIR (Fourier Transform Infrared Spectroscopy) on transmission mode after water filtration on 5 µm silicon filters. Thirty-eight WHC samples from the LWSS showed MPs up to 836 MPs/L, with an average value of 196 MPs/L. The most representative polymer was polyethylene (PE, 77.2%). The other eight polymers were also quantified. The length and width of MPs ranged between 84 µm and 41 µm, respectively. The AED of MPs ranged between 24 µm and 405 µm. The MP dimensions of both approaches can differ significantly.


Assuntos
Água Potável , Microplásticos , Poluentes Químicos da Água , Abastecimento de Água , Microplásticos/análise , Água Potável/análise , Água Potável/química , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Espectroscopia de Infravermelho com Transformada de Fourier , Tamanho da Partícula , Portugal
8.
BMC Bioinformatics ; 24(1): 439, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37990302

RESUMO

BACKGROUND: Cancer is a collection of diseases caused by the deregulation of cell processes, which is triggered by somatic mutations. The search for patterns in somatic mutations, known as mutational signatures, is a growing field of study that has already become a useful tool in oncology. Several algorithms have been proposed to perform one or both the following two tasks: (1) de novo estimation of signatures and their exposures, (2) estimation of the exposures of each one of a set of pre-defined signatures. RESULTS: Our group developed signeR, a Bayesian approach to both of these tasks. Here we present a new version of the software, signeR 2.0, which extends the possibilities of previous analyses to explore the relation of signature exposures to other data of clinical relevance. signeR 2.0 includes a user-friendly interface developed using the R-Shiny framework and improvements in performance. This version allows the analysis of submitted data or public TCGA data, which is embedded in the package for easy access. CONCLUSION: signeR 2.0 is a valuable tool to generate and explore exposure data, both from de novo or fitting analyses and is an open-source R package available through the Bioconductor project at ( https://doi.org/10.18129/B9.bioc.signeR ).


Assuntos
Neoplasias , Humanos , Teorema de Bayes , Neoplasias/genética , Mutação , Software , Algoritmos
9.
Bioinformatics ; 38(7): 1809-1815, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35104309

RESUMO

MOTIVATION: Despite of the fast development of highly effective vaccines to control the current COVID-19 pandemics, the unequal distribution and availability of these vaccines worldwide and the number of people infected in the world lead to the continuous emergence of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) variants of concern. Therefore, it is likely that real-time genomic surveillance will be continuously needed as an unceasing monitoring tool, necessary to follow the spread of the disease and the evolution of the virus. In this context, new genomic variants of SARS-CoV-2, including variants refractory to current vaccines, makes genomic surveillance programs tools of utmost importance. Nevertheless, the lack of appropriate analytical tools to quickly and effectively access the viral composition in meta-transcriptomic sequencing data, including environmental surveillance, represent possible challenges that may impact the fast adoption of this approach to mitigate the spread and transmission of viruses. RESULTS: We propose a statistical model for the estimation of the relative frequencies of SARS-CoV-2 variants in pooled samples. This model is built by considering a previously defined selection of genomic polymorphisms that characterize SARS-CoV-2 variants. The methods described here support both raw sequencing reads for polymorphisms-based markers calling and predefined markers in the variant call format. Results obtained using simulated data show that our method is quite effective in recovering the correct variant proportions. Further, results obtained by considering longitudinal data from wastewater samples of two locations in Switzerland agree well with those describing the epidemiological evolution of COVID-19 variants in clinical samples of these locations. Our results show that the described method can be a valuable tool for tracking the proportions of SARS-CoV-2 variants in complex mixtures such as waste water and environmental samples. AVAILABILITY AND IMPLEMENTATION: http://github.com/rvalieris/LCS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Perfilação da Expressão Gênica , Genômica
10.
Fish Shellfish Immunol ; 141: 109009, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37598735

RESUMO

Thioredoxin-like protein 1 (TXNL1) is a redox-active protein belonging to the thioredoxin family, which mainly controls the redox status of cells. The TXNL1 gene from Amphiprion clarkii (AcTXNL1) was obtained from a pre-established transcriptome database. The AcTXNL1 is encoded with 289 amino acids and is predominantly localized in the cytoplasm and nucleus. The TXN domain of AcTXNL1 comprises a34CGPC37 motif with redox-reactive thiol (SH-) groups. The spatial distribution pattern of AcTXNL1 mRNA was examined in different tissues, and the muscle was identified as the highest expressed tissue. AcTXNL1 mRNA levels in the blood and gills were significantly increased in response to different immunostimulants. In vitro antioxidant capacity of the recombinant AcTXNL1 protein (rACTXNL1) was evaluated using the ABTS free radical-scavenging activity assay, cupric ion reducing antioxidant capacity assay, turbidimetric disulfide reduction assay, and DNA nicking protection assay. The potent antioxidant activity of rAcTXNL1 exhibited a concentration-dependent manner in all assays. Furthermore, in the cellular environment, overexpression of AcTXNL1 increased cell viability under H2O2 stress and reduced nitric oxide (NO) production induced by lipopolysaccharides (LPS). Collectively, the experimental results revealed that AcTXNL1 is an antioxidant and immunologically important gene in A. clarkii.


Assuntos
Antioxidantes , Peróxido de Hidrogênio , Animais , Antioxidantes/metabolismo , Sequência de Aminoácidos , Proteínas de Peixes/química , Proteínas Recombinantes/genética , Tiorredoxinas/genética , Tiorredoxinas/química , RNA Mensageiro
11.
Int J Mol Sci ; 24(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36674930

RESUMO

Acute kidney injury (AKI) is a common and devastating pathologic condition, associated with considerable high morbidity and mortality. Although significant breakthroughs have been made in recent years, to this day no effective pharmacological therapies for its treatment exist. AKI is known to be connected with intrarenal and systemic inflammation. The innate immune system plays an important role as the first defense response mechanism to tissue injury. Toll-like receptor 4 (TLR4) is a well-characterized pattern recognition receptor, and increasing evidence has shown that TLR4 mediated inflammatory response, plays a pivotal role in the pathogenesis of acute kidney injury. Pathogen-associated molecular patterns (PAMPS), which are the conserved microbial motifs, are sensed by these receptors. Endogenous molecules generated during tissue injury, and labeled as damage-associated molecular pattern molecules (DAMPs), also activate pattern recognition receptors, thereby offering an understanding of sterile types of inflammation. Excessive, uncontrolled and/or sustained activation of TLR4, may lead to a chronic inflammatory state. In this review we describe the role of TLR4, its endogenous ligands and activation in the inflammatory response to ischemic/reperfusion-induced AKI and sepsis-associated AKI. The potential regeneration signaling patterns of TLR4 in acute kidney injury, are also discussed.


Assuntos
Injúria Renal Aguda , Receptor 4 Toll-Like , Humanos , Injúria Renal Aguda/patologia , Inflamação/patologia , Receptores de Reconhecimento de Padrão/fisiologia , Transdução de Sinais , Rim/patologia
12.
Biol Sport ; 40(1): 193-200, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36636185

RESUMO

We aimed to evaluate the effect of 4 weeks of plyometric training (PT), performed in the pre-competitive period, on the vertical jump performance of professional volleyball athletes. We recruited 17 professional female volleyball players (age: 19 ± 3 years; weight: 67.2 ± 5.50 kg; height: 1.81 ± 0.22 m; body fat: 14.4 ± 2.12%; squat 1RM test: 75.5 ± 7.82 kg; training time experience: 6.2 ± 3.4 years) to participate in four weeks of training and assessments. They were divided into an experimental group (EG = 9) and a control group (CG = 8). Both groups were submitted to friendly matches, technical, tactical and resistance training (4 weeks/˜9 sessions per week), and internal load monitoring was carried out. The EG performed PT twice a week. At the beginning and end of the four weeks, jump tests were performed. The main findings are: 1) PT when incorporated into the pre-competitive period can induce greater improvements in jumping performance (EG = 28.93 ± 3.24 cm to 31.67 ± 3.39 cm; CG = 27.91 ± 4.64 cm to 28.97 ± 4.58 cm; when comparing the percentage delta, we found a difference between groups with ES of 1.04 and P = 0.02); 2) this result is observed when the training load is similar between groups and increases over the weeks, respecting the linear progression principle. Therefore, including plyometric training in the preparatory period for volleyball, with low monotony and training strain increment, is an effective strategy for further CMJ performance improvement.

13.
J Biol Chem ; 296: 100586, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33774050

RESUMO

Previous work has suggested that highly positively charged protein segments coded by rare codons or poly (A) stretches induce ribosome stalling and translational arrest through electrostatic interactions with the negatively charged ribosome exit tunnel, leading to inefficient elongation. This arrest leads to the activation of the Ribosome Quality Control (RQC) pathway and results in low expression of these reporter proteins. However, the only endogenous yeast proteins known to activate the RQC are Rqc1, a protein essential for RQC function, and Sdd1, a protein with unknown function, both of which contain polybasic sequences. To explore the generality of this phenomenon, we investigated whether the RQC complex controls the expression of other proteins with polybasic sequences. We showed by ribosome profiling data analysis and western blot that proteins containing polybasic sequences similar to, or even more positively charged than those of Rqc1 and Sdd1, were not targeted by the RQC complex. We also observed that the previously reported Ltn1-dependent regulation of Rqc1 is posttranslational, independent of the RQC activity. Taken together, our results suggest that RQC should not be regarded as a general regulatory pathway for the expression of highly positively charged proteins in yeast.


Assuntos
Ribossomos/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/metabolismo , Expressão Gênica , Ligação Proteica , Saccharomyces cerevisiae/genética
14.
J Comput Chem ; 43(19): 1298-1312, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35638694

RESUMO

We report here for the first time the potential energy surfaces (PES) of phenyletilamine (PEA) and meta-tyramine (m-OH-PEA) at the D2 dopamine receptor (D2DR) binding site. PESs not only allow us to observe all the critical points of the surface (minimums, maximums, and transition states), but also to note the ease or difficulty that each local minima have for their conformational inter-conversions and therefore know the conformational flexibility that these ligands have in their active sites. Taking advantage of possessing this valuable information, we analyze how accurate a standard docking study is in these cases. Our results indicate that although we have to be careful in how to carry out this type of study and to consider performing some extra-simulations, docking calculations can be satisfactory. In order to analyze in detail the different molecular interactions that are stabilizing the different ligand-receptor (L-R) complexes, we carried out quantum theory of atoms in molecules (QTAIM) computations and NMR shielding calculations. Although some of these techniques are a bit tedious and require more computational time, our results demonstrate the importance of performing computational simulations using different types of combined techniques (docking/MD/hybrid QM-MM/QTAIM and NMR shielding calculations) in order to obtain more accurate results. Our results allow us to understand in details the molecular interactions stabilizing and destabilizing the different L-R complexes reported here. Thus, the different activities observed for dopamine (DA), m-OH-PEA, and PEA can be clearly explained at molecular level.


Assuntos
Dopamina , Teoria Quântica , Sítios de Ligação , Domínio Catalítico , Ligantes , Simulação de Acoplamento Molecular , Ligação Proteica
15.
BMC Cardiovasc Disord ; 22(1): 559, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36550397

RESUMO

BACKGROUND: Atrial fibrillation (AF) negatively impacts health systems worldwide. We aimed to capture perceptions of and barriers and facilitators for AF care in Brazilian primary care units (PCUs) from the perspective of healthcare professionals (HCPs). METHODS: This mixed-methods, cross-sectional study utilised an exploratory sequential design, beginning with the quantitative data collection (up to 18 closed questions) immediately followed by a semi-structured interview. HCPs were recruited from 11 PCUs in the Sao Paulo region and included managers, physicians, pharmacists, nurses and community health agents. Descriptive statistics were used to present findings from the quantitative questionnaire and inductive analysis was used to identify themes from the qualitative data. RESULTS: One hundred seven HCPs were interviewed between September 2019 and May 2020. Three main themes were identified that encapsulated barriers and facilitators to AF care: access to care (appointments, equipment/tests and medication), HCP and patient roles (HCP/patient relationship and patient adherence) and the role of the organisation/system (infrastructure, training and protocols/guidelines). Findings from the qualitative analysis reinforced the quantitative findings, including a lack of AF-specific training for HCPs, protocols/guidelines on AF management, INR tests in the PCUs, patient knowledge of AF management and novel oral anticoagulants (NOACs) as key barriers to optimal AF care. CONCLUSIONS: Development and implementation of AF-specific training for PCU HCPs are needed in Brazil, along with evidence-based protocols and guidelines, educational programmes for patients, better access to INR tests for patients taking warfarin and availability of NOACs.


Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Brasil , Estudos Transversais , Administração Oral , Anticoagulantes/efeitos adversos , Pessoal de Saúde , Atenção Primária à Saúde
16.
Ann Noninvasive Electrocardiol ; 27(2): e12917, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34882891

RESUMO

BACKGROUND: Brugada syndrome (BrS) is somewhat a challenging diagnosis, due to its dynamic pattern. One of the aspects of this disease is a significant conduction disorder located in the right ventricular outflow tract (RVOT), which can be explained as a consequence of low expression of Connexin-43. This decreased conduction speed is responsible for the typical electrocardiographic pattern. Opposite leads located preferably in inferior leads of the electrocardiogram may show a deep and widened S wave associated with ascending ST segment depression. Holter monitoring electrocardiographic (ECG) aspects is still a new frontier of knowledge in BrS, especially in intermittent clinical presentations. METHODS: We describe, as an exploratory analysis, five case series of intermittent type 1 BrS to demonstrate the appearance of ascending ST segment depression and widening of the S wave, during 3-channel 24h-Holter monitoring (C1, C2 and C3) with bipolar leads. RESULTS: In the five cases described, the ST segment depression was observed mainly in C2, but in some cases also in C1 and C3. Only case 1 presented concomitant intermittent elevation of the ST segment in C1. All cases were intermittent. CONCLUSION: The recognition of an ECG pattern with ascending ST-segment depression and widening of the S wave in 3-channel Holter described in this case series should raise a suspicion of the BrS and suggests the counterpart of a dromotropic disturbance registered in the RVOT and/or reciprocal changes.


Assuntos
Síndrome de Brugada , Arritmias Cardíacas , Depressão , Eletrocardiografia , Eletrocardiografia Ambulatorial , Humanos
17.
BMC Med Inform Decis Mak ; 22(1): 40, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35168629

RESUMO

INTRODUCTION: Syphilis is a sexually transmitted disease (STD) caused by Treponema pallidum subspecies pallidum. In 2016, it was declared an epidemic in Brazil due to its high morbidity and mortality rates, mainly in cases of maternal syphilis (MS) and congenital syphilis (CS) with unfavorable outcomes. This paper aimed to mathematically describe the relationship between MS and CS cases reported in Brazil over the interval from 2010 to 2020, considering the likelihood of diagnosis and effective and timely maternal treatment during prenatal care, thus supporting the decision-making and coordination of syphilis response efforts. METHODS: The model used in this paper was based on stochastic Petri net (SPN) theory. Three different regressions, including linear, polynomial, and logistic regression, were used to obtain the weights of an SPN model. To validate the model, we ran 100 independent simulations for each probability of an untreated MS case leading to CS case (PUMLC) and performed a statistical t-test to reinforce the results reported herein. RESULTS: According to our analysis, the model for predicting congenital syphilis cases consistently achieved an average accuracy of 93% or more for all tested probabilities of an untreated MS case leading to CS case. CONCLUSIONS: The SPN approach proved to be suitable for explaining the Notifiable Diseases Information System (SINAN) dataset using the range of 75-95% for the probability of an untreated MS case leading to a CS case (PUMLC). In addition, the model's predictive power can help plan actions to fight against the disease.


Assuntos
Sífilis Congênita , Sífilis , Brasil/epidemiologia , Feminino , Humanos , Sistemas de Informação , Gravidez , Cuidado Pré-Natal , Sífilis/diagnóstico , Sífilis/epidemiologia , Sífilis Congênita/diagnóstico , Sífilis Congênita/epidemiologia
18.
J Sci Food Agric ; 102(4): 1736-1743, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34403496

RESUMO

BACKGROUND: Bread represents a significant share of food waste worldwide. The extension of the bread shelf life together with innovative systems of food waste treatment might decrease waste biomass decay, the need for transportation, and the need for storage. In recent years, insects have been selected as a valuable tool for food waste treatment owing to their capability to transform low-value food waste into biomass with high nutritional value. Bakery wastes can be used profitably for this purpose. This work had two objectives: (i) to measure the impact of flaxseed cake fortification on bread shelf life depending on the leavening agent (baker's yeast vs sourdough); (ii) to evaluate the possible reuse of the stale bread fortified with flaxseed cake for Tenebrio molitor rearing. RESULTS: Our results showed that fortification seemed to slow the hardening rate of bread, particularly if baker's yeast was used. The time necessary for mold to appear in sourdough bread doubled (from 2 to 4 days). The addition of flaxseed cake to the recipe determined an increase of its scrap consumption by T. molitor larvae. We also observed a significant increase in the body mass of the T. molitor larvae fed with bread obtained with the brewer's yeast with respect to larvae fed with the sourdough. CONCLUSION: Taken together, these preliminary data can indicate that sourdough bread fortified with 5% of flaxseed cake can represent a promising tool to reduce food waste and to recycle bread scraps by a novel zero-waste approach. © 2021 Society of Chemical Industry.


Assuntos
Linho , Eliminação de Resíduos , Tenebrio , Animais , Pão , Fermentação , Larva
19.
Environ Monit Assess ; 194(11): 824, 2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36152067

RESUMO

The Metropolitan Region of Recife, the capital of the state of Pernambuco in northeastern Brazil, has a high demographic density and developed under a region of marine phosphorus with high concentrations of phosphate that naturally contains uranium ore, producing ionizing radiation from descendants of the radioisotope 238U where 226Ra and 210Pb are of great importance in verifying the probable harmful effects on human health due to environmental radioactivity. The supply of drinking water is the responsibility of the state-owned company COMPESA which uses wells of great depth to complete the supply of drinking water for the entire population. COMPESA and the RAE Group of the Federal University of Pernambuco developed a joint project to assess the concentrations of 226Ra and 210Pb and estimate the equivalent and effective doses caused by ingesting these radiation sources. According to the above, this research aimed to evaluate concentrations of 226Ra and 210Pb in drinking water samples from 110 deep wells in Recife. The activities of 226Ra and 210Pb ranged from 1.4 ± 0.3 to 119.3 ± 12.9 and from 25.6 ± 3.3 to 563.2 ± 45.6 mBq.L-1, with arithmetic means of 48.1 ± 3.8 and 231.1 ± 20 mBq.L-1, respectively. The equivalent doses average in bone tissue due to 226Ra and 210Pb were 0.45 ± 0.04 and 3.9 ± 0.37 mSv.y-1, and the annual average effective doses were 0.01 ± 0.00 and 0.13 ± 0.01 mSv.y-1, respectively.


Assuntos
Água Potável , Monitoramento de Radiação , Urânio , Poluentes Radioativos da Água , Brasil , Humanos , Chumbo , Fosfatos , Fósforo , Radioisótopos/análise , Urânio/análise , Poluentes Radioativos da Água/análise , Abastecimento de Água
20.
Hum Mutat ; 42(3): 290-299, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33326660

RESUMO

The current study aimed to identify new breast and/or ovarian cancer predisposition genes. For that, whole-exome sequencing (WES) was performed in the germline DNA of 52 non-BRCA1/BRCA2/TP53 mutation carrier women at high-risk for hereditary breast and ovarian cancer (HBOC). All variants were classified using information from population and disease specific databases, in silico prediction tools and the American College of Medical Genetics and Genomics (ACMG) criteria. Loss of heterozygosity (LOH) of tumor samples and segregation analyses were performed whenever possible. The variants identified were investigated in a second, independent cohort of 17 BC cases. Pathogenic/Likely Pathogenic variants were identified in known cancer genes such as CHEK2, MUTYH, PMS2, and RAD51C. Rare and potentially pathogenic variants were identified in DNA repair genes (FAN1, POLQ, and RAD54L) and other cancer-related genes such as DROSHA and SLC34A2. Interestingly, the variant c.149T>G in the FAN1 gene was identified in two unrelated families, and exhibited LOH in the tumor tissue of one of them. In conclusion, this is the largest Brazilian WES study involving families at high-risk for HBOC which has brought novel insights into the role of potentially new genetic risk factors for hereditary breast and ovarian cancer.


Assuntos
Neoplasias da Mama , Síndrome Hereditária de Câncer de Mama e Ovário , Neoplasias Ovarianas , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/patologia , Feminino , Genes BRCA2 , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Humanos , Perda de Heterozigosidade , Mutação , Neoplasias Ovarianas/genética , Sequenciamento do Exoma
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