RESUMO
Candida albicans is one of the agents of invasive candidiasis, a life-threatening disease strongly associated with hospitalization, particularly among patients in intensive care units with central venous catheters. This study aimed to evaluate the synergistic activity of the antifungal peptide ToAP2 combined with fluconazole against C. albicans biofilms grown on various materials. We tested combinations of different concentrations of the peptide ToAP2 with fluconazole on C. albicans biofilms. These biofilms were generated on 96-well plates, intravenous catheters, and infusion tubes in RPMI medium at two maturation stages. Scanning electron microscopy and atomic force microscopy were employed to assess the biofilm structure. We also evaluated the expression of genes previously proven to be involved in C. albicans biofilm formation in planktonic and biofilm cells after treatment with the peptide ToAP2 using qPCR. ToAP2 demonstrated a synergistic effect with fluconazole at concentrations up to 25 µM during both the early and mature stages of biofilm formation in 96-well plates and on medical devices. Combinations of 50, 25, and 12.5 µM of ToAP2 with 52 µM of fluconazole significantly reduced the biofilm viability compared to individual treatments and untreated controls. These results were supported by substantial structural changes in the biofilms observed through both scanning and atomic force microscopy. The gene expression analysis of C. albicans cells treated with 25 µM of ToAP2 revealed a decrease in the expression of genes associated with membrane synthesis, along with an increase in the expression of genes involved in efflux pumps, adhesins, and filamentation. Our results highlight the efficacy of the combined ToAP2 and fluconazole treatment against C. albicans biofilms. This combination not only shows therapeutic potential but also suggests its utility in developing preventive biofilm tools for intravenous catheters.
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Antifúngicos , Biofilmes , Candida albicans , Sinergismo Farmacológico , Fluconazol , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Fluconazol/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Antifúngicos/farmacologia , Peptídeos Antimicrobianos/farmacologia , Testes de Sensibilidade Microbiana , Humanos , Microscopia de Força Atômica , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismoRESUMO
BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is a well-established treatment for severe cardio-pulmonary failure. The use of large bore cannulas in the femoral vessels for an extended period has been associated with significant wound complications. There is a lack of data analyzing risk factors that can mitigate such complications. The primary purpose of this study was to identify modifiable risk factors associated with femoral wound complications after VA ECMO decannulation. METHODS: Retrospective analysis of wound complications in patients following VA ECMO decannulation from 2014-2021 at a single academic institution were analyzed. Wound complications were defined as wound infection, dehiscence, or those wounds that were deliberately opened to promote healing by secondary intention. RESULTS: Sixty patients underwent decannulation of VA ECMO with operative repair of the femoral artery. Fifteen patients were identified to have wound complications, eight (53%) of these had infection. Fourteen (93%) patients had wound dehiscence or had their wound purposely opened at bedside. Univariate analysis revealed no association of access-related complication with higher Body Mass Index (BMI, 28.3 vs. 32.7 kg/m2, P=0.110) but here was a trend in having more wound complications in individuals with COVID-19 infection (6.7% vs. 26.7%, P=0.058). Patients that had dual cannulation with the arterial and venous cannulas in the same groin had significantly more wound complications compared to single cannulation arterial and venous cannulas in separate groins (57.8% vs. 93.3%; P=0.012). Multivariate analysis revealed same side cannulation (OR 18.05, 95% CI 1.44-226.18, P=0.025) and COVID-19 infection (OR 18.18, 95% CI 1.50-220.66, P=0.023) were independent predictors of wound complications. CONCLUSIONS: Wound complications after VA ECMO decannulation is associated with COVID-19 infection and having venous and arterial cannulas in the same groin. We recommend that the arterial and venous cannulation be placed in different groins in patients that require VA ECMO.
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COVID-19 , Remoção de Dispositivo , Oxigenação por Membrana Extracorpórea , Artéria Femoral , Humanos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , COVID-19/terapia , Fatores de Risco , Artéria Femoral/cirurgia , Cateterismo Periférico/efeitos adversos , Deiscência da Ferida Operatória/etiologia , Idoso , Adulto , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/terapia , Infecção da Ferida Cirúrgica/diagnósticoRESUMO
BACKGROUND: Genotyping and amyloid fibril detection in tissues are generally considered the diagnostic gold standard in transthyretin-related amyloidosis. Patients carry less stable TTR homotetramers prone to dissociation into non-native monomers, which rapidly self-assemble into oligomers and, ultimately, amyloid fibrils. Thus, the initial event of the amyloid cascade produces the smallest transthyretin species: the monomers. This creates engineering opportunities for diagnosis that remain unexplored. METHODS: We hypothesise that molecular sieving represents a promising method for isolating and concentrating trace TTR monomers from the tetramers present in plasma samples. Subsequently, immunodetection can be utilised to distinguish monomeric TTR from other low molecular weight proteins within the adsorbed fraction. A two-step assay was devised (ImmunoSieve assay), combining molecular sieving and immunodetection for sensing monomeric transthyretin. This assay was employed to analyse plasma microsamples from 10 individuals, including 5 pre-symptomatic carriers of TTR-V30M, the most prevalent amyloidosis-associated TTR variant worldwide, and 5 healthy controls. RESULTS: The ImmunoSieve assay enable sensitive detection of monomeric transthyretin in plasma microsamples. Moreover, the circulating monomeric TTR levels were significantly higher in carriers of amyloidogenic TTR mutation. CONCLUSIONS: Monomeric TTR can function as a biomarker for evaluating disease progression and assessing responses to therapies targeted at stabilising native TTR.
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Neuropatias Amiloides Familiares , Biomarcadores , Pré-Albumina , Humanos , Pré-Albumina/genética , Pré-Albumina/metabolismo , Neuropatias Amiloides Familiares/sangue , Neuropatias Amiloides Familiares/genética , Neuropatias Amiloides Familiares/diagnóstico , Biomarcadores/sangue , Masculino , Feminino , Amiloide/sangue , Amiloide/metabolismo , Amiloide/genética , MutaçãoRESUMO
BACKGROUND: Postoperative myocardial infarction (POMI) is associated with major surgeries and remains the leading cause of mortality and morbidity in people undergoing vascular surgery, with an incidence rate ranging from 5% to 20%. Preoperative coronary interventions, such as coronary artery bypass grafting (CABG) or percutaneous coronary interventions (PCI), may help prevent acute myocardial infarction in the perioperative period of major vascular surgery when used in addition to routine perioperative drugs (e.g. statins, angiotensin-converting enzyme inhibitors, and antiplatelet agents), CABG by creating new blood circulation routes that bypass the blockages in the coronary vessels, and PCI by opening up blocked blood vessels. There is currently uncertainty around the benefits and harms of preoperative coronary interventions. OBJECTIVES: To assess the effects of preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery. SEARCH METHODS: We searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, and CINAHL EBSCO on 13 March 2023. We also searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) or quasi-RCTs that compared the use of preoperative coronary interventions plus usual care versus usual care for preventing acute myocardial infarction during major open vascular or endovascular surgery. We included participants of any sex or any age undergoing major open vascular surgery, major endovascular surgery, or hybrid vascular surgery. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes of interest were acute myocardial infarction, all-cause mortality, and adverse events resulting from preoperative coronary interventions. Our secondary outcomes were cardiovascular mortality, quality of life, vessel or graft secondary patency, and length of hospital stay. We reported perioperative and long-term outcomes (more than 30 days after intervention). We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included three RCTs (1144 participants). Participants were randomised to receive either preoperative coronary revascularisation with PCI or CABG plus usual care or only usual care before major vascular surgery. One trial enrolled participants if they had no apparent evidence of coronary artery disease. Another trial selected participants classified as high risk for coronary disease through preoperative clinical and laboratorial testing. We excluded one trial from the meta-analysis because participants from both the control and the intervention groups were eligible to undergo preoperative coronary revascularisation. We identified a high risk of performance bias in all included trials, with one trial displaying a high risk of other bias. However, the risk of bias was either low or unclear in other domains. We observed no difference between groups for perioperative acute myocardial infarction, but the evidence is very uncertain (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.02 to 4.57; 2 trials, 888 participants; very low-certainty evidence). One trial showed a reduction in incidence of long-term (> 30 days) acute myocardial infarction in participants allocated to the preoperative coronary interventions plus usual care group, but the evidence was very uncertain (RR 0.09, 95% CI 0.03 to 0.28; 1 trial, 426 participants; very low-certainty evidence). There was little to no effect on all-cause mortality in the perioperative period when comparing the preoperative coronary intervention plus usual care group to usual care alone, but the evidence is very uncertain (RR 0.79, 95% CI 0.31 to 2.04; 2 trials, 888 participants; very low-certainty evidence). The evidence is very uncertain about the effect of preoperative coronary interventions on long-term (follow up: 2.7 to 6.2 years) all-cause mortality (RR 0.74, 95% CI 0.30 to 1.80; 2 trials, 888 participants; very low-certainty evidence). One study reported no adverse effects related to coronary angiography, whereas the other two studies reported five deaths due to revascularisations. There may be no effect on cardiovascular mortality when comparing preoperative coronary revascularisation plus usual care to usual care in the short term (RR 0.07, 95% CI 0.00 to 1.32; 1 trial, 426 participants; low-certainty evidence). Preoperative coronary interventions plus usual care in the short term may reduce length of hospital stay slightly when compared to usual care alone (mean difference -1.17 days, 95% CI -2.05 to -0.28; 1 trial, 462 participants; low-certainty evidence). We downgraded the certainty of the evidence due to concerns about risk of bias, imprecision, and inconsistency. None of the included trials reported on quality of life or vessel graft patency at either time point, and no study reported on adverse effects, cardiovascular mortality, or length of hospital stay at long-term follow-up. AUTHORS' CONCLUSIONS: Preoperative coronary interventions plus usual care may have little or no effect on preventing perioperative acute myocardial infarction and reducing perioperative all-cause mortality compared to usual care, but the evidence is very uncertain. Similarly, limited, very low-certainty evidence shows that preoperative coronary interventions may have little or no effect on reducing long-term all-cause mortality. There is very low-certainty evidence that preoperative coronary interventions plus usual care may prevent long-term myocardial infarction, and low-certainty evidence that they may reduce length of hospital stay slightly, but not cardiovascular mortality in the short term, when compared to usual care alone. Adverse effects of preoperative coronary interventions were poorly reported in trials. Quality of life and vessel or graft patency were not reported. We downgraded the certainty of the evidence most frequently for high risk of bias, inconsistency, or imprecision. None of the analysed trials provided significant data on subgroups of patients who could potentially experience more substantial benefits from preoperative coronary intervention (e.g. altered ventricular ejection fraction). There is a need for evidence from larger and homogeneous RCTs to provide adequate statistical power to assess the role of preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery.
Assuntos
Ponte de Artéria Coronária , Procedimentos Endovasculares , Infarto do Miocárdio , Intervenção Coronária Percutânea , Complicações Pós-Operatórias , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/mortalidade , Intervenção Coronária Percutânea/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Ponte de Artéria Coronária/métodos , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade , Cuidados Pré-Operatórios/métodos , Viés , Período Perioperatório , Tempo de InternaçãoRESUMO
The adaptation of amphibians to diverse environments is closely related to the characteristics of their skin. The complex glandular system of frog skin plays a pivotal role in enabling these animals to thrive in both aquatic and terrestrial habitats and consists of crucial functions such as respiration and water balance as well as serving as a defensive barrier due to the secretion of bioactive compounds. We herein report the first investigation on the skin secretion of Odontophrynus americanus, as a potential source of bioactive peptides and also as an indicator of its evolutionary adaptations to changing environments. Americanin-1 was isolated and identified as a neutral peptide exhibiting moderate antibacterial activity against E. coli. Its amphipathic sequence including 19 amino acids and showing a propensity for α-helix structure is discussed. Comparisons of the histomorphology of the skin of O. americanus with other previously documented species within the same genus revealed distinctive features in the Patagonian specimen, differing from conspecifics from other Argentine provinces. The presence of the Eberth-Katschenko layer, a prevalence of iridophores, and the existence of glycoconjugates in its serous glands suggest that the integument is adapted to retain skin moisture. This adaptation is consistent with the prevailing aridity of its native habitat.
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Anuros , Pele , Animais , Pele/química , Escherichia coli/efeitos dos fármacos , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Estrutura Molecular , Argentina , Peptídeos/química , Peptídeos/farmacologia , Sequência de Aminoácidos , Testes de Sensibilidade MicrobianaRESUMO
This study aimed to assess two homogenization methods to recover norovirus from Minas artisanal cheese (MAC) made with raw bovine milk obtained from four microregions of the Minas Gerais state, Brazil, with different ripening times and geographical and abiotic characteristics. For this purpose, 33 fiscal samples were artificially contaminated with norovirus GI and GII, and Mengovirus (MgV), used as an internal process control (IPC). TRIzol® reagent and Proteinase K homogenization methods were evaluated for all samples were then subjected to RNA extraction using viral magnetic beads and RT-qPCR Taqman® for viral detection/quantification. Proteinase K method showed better efficiency results for both norovirus GI and GII, with means recovery efficiency of 45.7% (95% CI 34.3-57.2%) and 41.4% (95% CI 29.1-53.6%), respectively, when compared to TRIzol method (16.6% GI, 95% CI 8.4-24.9%, and 12.3% GII, 95% CI 7.0-17.6%). The limits of detection for norovirus GI and GII for this method were 101GC/g and 103GC/g, respectively, independent of cheese origin. MgV was detected and revealed in 100% success rate in all types of cheese, with mean recovery efficiency of 25.6% for Proteinase K, and 3.8% for the TRIzol method. According to cheese origin, Triangulo Mineiro MAC had the highest mean recovery rates for the three viral targets surveyed (89% GI, 87% GII, and 51% MgV), while Serro MAC showed the lowest rates (p < 0.001). Those results indicate that the proteinase K adapted method is suitable for norovirus GI and GII detection in MAC and corroborated MgV as an applicable IPC to be used during the process.
Assuntos
Queijo , Contaminação de Alimentos , Leite , Norovirus , Queijo/virologia , Norovirus/isolamento & purificação , Norovirus/genética , Norovirus/classificação , Animais , Leite/virologia , Bovinos , Brasil , Contaminação de Alimentos/análise , RNA Viral/isolamento & purificação , RNA Viral/genética , RNA Viral/análise , Fast Foods/virologia , Fast Foods/análiseRESUMO
Snake venoms contain various bradykinin-potentiating peptides (BPPs). First studied for their vasorelaxant properties due to angiotensin converting enzyme (ACE) inhibition, these molecules present a range of binding partners, among them the argininosuccinate synthase (AsS) enzyme. This has renewed interest in their characterization from biological sources and the evaluation of their pharmacological activities. In the present work, the low molecular weight fraction of Bothrops moojeni venom was obtained and BPPs were characterized by mass spectrometry. Eleven BPPs or related peptides were sequenced, and one of them, BPP-Bm01, was new. Interestingly, some oxidized BPPs were detected. The three most abundant peptides were BPP-Bm01, BPP-Bax12, and BPP-13a, and their putative interactions with the AsS enzyme were investigated in silico. A binding cavity for these molecules was predicted, and docking studies allowed their ranking. Three peptides were synthesized and submitted to vasorelaxation assays using rat aortic rings. While all BPPs were active, BPP-Bm01 showed the highest potency in this assay. This work adds further diversity to BPPs from snake venoms and suggests, for the first time, a putative binding pocket for these molecules in the AsS enzyme. This can guide the design of new and more potent AsS activators.
Assuntos
Aorta , Bothrops , Oligopeptídeos , Peptídeos , Serpentes Peçonhentas , Animais , Ratos , Brasil , Aorta/efeitos dos fármacos , Peptídeos/farmacologia , Peptídeos/química , Bradicinina/farmacologia , Masculino , Venenos de Crotalídeos/farmacologia , Venenos de Crotalídeos/química , Ratos Wistar , Venenos de Serpentes/farmacologia , Vasodilatadores/farmacologia , Vasodilatadores/química , Estrutura MolecularRESUMO
This study investigated the prevalence and genetic diversity of gastroenteric viruses in mussels and oysters in Rio de Janeiro, Brazil. One hundred and thirty-four marketed bivalve samples were obtained between January and December 2022. The viral analysis was performed according to ISO/TS 15216, and the screening revealed the detection of norovirus GII/GI (40.3%), sapovirus (SaV; 12.7%), human mastadenovirus (7.5%), and rotavirus A (RVA; 5.9%). In total, 44.8% (60) of shellfish samples tested positive for one or more viruses, 46.7% (28/60) of the positive samples tested positive for a single viral agent, 26.7% (16) tested positive for two viral agents, 8.3% (5) for three viral agents, and 13.3% (8) for four viral agents. Additionally, three mussel samples were contaminated with the five investigated viruses (5%, 3/60). Norovirus GII showed the highest mean viral load (3.4 × 105 GC/g), followed by SaV (1.4 × 104 GC/g), RVA (1.1 × 104 GC/g), human mastadenovirus (3.9 × 103 GC/g), and norovirus GI (6.7 × 102 GC/g). Molecular characterization revealed that the recovered norovirus strains belonged to genotypes GII.2, GII.6, GII.9, GII.17, and GII.27; SaV belonged to genotypes GI.1 and GIV.1; RVA to genotypes G6, G8, P[8]-III, and human mastadenovirus to types F40 and F41. The GII.27 norovirus characterized in this study is the only strain of this genotype reported in Brazil. This study highlights the dissemination and diversity of gastroenteric viruses present in commercialized bivalves in a touristic area, indicating the potential risk to human health and the contribution of bivalves in the propagation of emerging pathogens.
Assuntos
Bivalves , Infecções por Caliciviridae , Mastadenovirus , Norovirus , Ostreidae , Rotavirus , Animais , Humanos , Brasil/epidemiologia , Cidades , Rotavirus/genética , Norovirus/genética , Genótipo , Filogenia , FezesRESUMO
BACKGROUND: Diabetes Mellitus (DM) is considered a chronic disease with numerous secondary complications that negatively affect the quality of life of patients. However, the specific, known and validated instruments for Brazilian Portuguese are too extensive, which often makes their use infeasible. OBJECTIVE: To validate the internal structure of the Brazilian version of the Diabetes Quality of Life (DQOL) measure. METHODOLOGY: Patients with DM type 1 or 2, between the ages of 18 and 76, were evaluated between April 2022 and May 2022. The survey was conducted online using the Google Forms platform. The original DQOL contains 46 multiple-choice questions organized into four domains. For structural validity, confirmatory factor analysis (CFA) was performed using RStudio software (Boston, MA, USA) with the packages lavaan and semPlot. RESULTS: A total of 354 subjects were evaluated. The 3-domain, 24-item version of the DQOL was the most adequate, with acceptable values for all fit indices (chi-square/GL < 3, TLI and CFI > 0.90, and RMSEA and SRMR < 0.08). CONCLUSION: The structure with three domains and 24 items is the most appropriate based on factor analysis. The Brazilian version of the DQOL with a structure of 3 domains and 24 items has adequate measurement properties that support its use in the clinical and scientific context in patients with DM.
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Diabetes Mellitus Tipo 1 , Qualidade de Vida , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Brasil , Inquéritos e Questionários , Idioma , Psicometria , Reprodutibilidade dos TestesRESUMO
Amyloidosis is a group of protein misfolding diseases, which include spongiform encephalopathies, Alzheimer's disease and transthyretin (TTR) amyloidosis; all of them are characterized by extracellular deposits of an insoluble fibrillar protein. TTR amyloidosis is a highly debilitating and life-threatening disease. Patients carry less stable TTR homotetramers that are prone to dissociation into non-native monomers, which in turn rapidly self-assemble into oligomers and, ultimately, amyloid fibrils. Liver transplantation to induce the production of wild-type TTR was the only therapeutic strategy until recently. A promising approach to ameliorate transthyretin (TTR) amyloidosis is based on the so-called TTR kinetic stabilizers. More than 1000 TTR stabilizers have already been tested by many research groups, but the diversity of experimental techniques and conditions used hampers an objective prioritization of the compounds. One of the most reliable and unambiguous techniques applied to determine the structures of the TTR/drug complexes is X-ray diffraction. Most of the potential inhibitors bind in the TTR channel and the crystal structures reveal the atomic details of the interaction between the protein and the compound. Here we suggest that the stabilization effect is associated with a compaction of the quaternary structure of the protein and propose a scoring function to rank drugs based on X-ray crystallography data.
Assuntos
Neuropatias Amiloides Familiares , Pré-Albumina , Humanos , Pré-Albumina/metabolismo , Cristalografia por Raios X , Neuropatias Amiloides Familiares/tratamento farmacológico , Amiloide/químicaRESUMO
The potential emergence of zoonotic diseases has raised significant concerns, particularly in light of the recent pandemic, emphasizing the urgent need for scientific preparedness. The bioprospection and characterization of new molecules are strategically relevant to the research and development of innovative drugs for viral and bacterial treatment and disease management. Amphibian species possess a diverse array of compounds, including antimicrobial peptides. This study identified the first bioactive peptide from Salamandra salamandra in a transcriptome analysis. The synthetic peptide sequence, which belongs to the defensin family, was characterized through MALDI TOF/TOF mass spectrometry. Molecular docking assays hypothesized the interaction between the identified peptide and the active binding site of the spike WT RBD/hACE2 complex. Although additional studies are required, the preliminary evaluation of the antiviral potential of synthetic SS-I was conducted through an in vitro cell-based SARS-CoV-2 infection assay. Additionally, the cytotoxic and hemolytic effects of the synthesized peptide were assessed. These preliminary findings highlighted the potential of SS-I as a chemical scaffold for drug development against COVID-19, hindering viral infection. The peptide demonstrated hemolytic activity while not exhibiting cytotoxicity at the antiviral concentration.
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Biotechnological advancements require the physicochemical alteration of molecules to enhance their biological efficacy for the effective treatment of gastric ulcers. The study aimed to produce a polyelectrolytic compound from red angico gum (AG) by carboxymethylation, evaluate its physicochemical characteristics and investigate gastric protection against ethanol-induced ulcers. AG and carboxymethylated angico gum (CAG) were characterized by Fourier transform infrared spectroscopy, determination of the degree of substitution and gel permeation chromatography (GPC) and 13C NMR techniques. The results demonstrated that the modification of the polymer was satisfactory, presenting conformational changes e improving the interaction with the gastric mucosa. AG and CAG reduced macroscopic and microscopic damage such as edema, hemorrhage and cell loss caused by exposure of the mucosa to alcohol. Both demonstrated antioxidant activity in vitro, and in vivo, pretreatment with gums led to the restoration of superoxide dismutase and glutathione levels compared to the injured group. Concurrently, the levels of malondialdehyde and nitrite decreased. Atomic force microscopy showed that CAG presented better conformational properties of affinity and protection with the gastric mucosa compared to AG in the acidic pH. Based on our findings, it is suggested that this compound holds promise as a prospective product for future biotechnological applications.
Assuntos
Colubrina , Fabaceae , Úlcera Gástrica , Estudos Prospectivos , Estômago , Antioxidantes/efeitos adversos , Mucosa Gástrica , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Extratos Vegetais/químicaRESUMO
The existence of encrypted fragments with antimicrobial activity in human proteins has been thoroughly demonstrated in the literature. Recently, algorithms for the large-scale identification of these segments in whole proteomes were developed, and the pervasiveness of this phenomenon was stated. These algorithms typically mine encrypted cationic and amphiphilic segments of proteins, which, when synthesized as individual polypeptide sequences, exert antimicrobial activity by membrane disruption. In the present report, the human reference proteome was submitted to the software kamal for the uncovering of protein segments that correspond to putative intragenic antimicrobial peptides (IAPs). The assessment of the identity of these segments, frequency, functional classes of parent proteins, structural relevance, and evolutionary conservation of amino acid residues within their corresponding proteins was conducted in silico. Additionally, the antimicrobial and anticancer activity of six selected synthetic peptides was evaluated. Our results indicate that cationic and amphiphilic segments can be found in 2% of all human proteins, but are more common in transmembrane and peripheral membrane proteins. These segments are surface-exposed basic patches whose amino acid residues present similar conservation scores to other residues with similar solvent accessibility. Moreover, the antimicrobial and anticancer activity of the synthetic putative IAP sequences was irrespective to whether these are associated to membranes in the cellular setting. Our study discusses these findings in light of the current understanding of encrypted peptide sequences, offering some insights into the relevance of these segments to the organism in the context of their harboring proteins or as separate polypeptide sequences.
Assuntos
Anti-Infecciosos , Proteoma , Humanos , Proteoma/genética , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/farmacologia , Sequência de Aminoácidos , AminoácidosRESUMO
Rotavirus is the most common pathogen causing pediatric diarrhea and an important cause of morbidity and mortality in low- and middle-income countries. Previous evidence suggests that the introduction of rotavirus vaccines in national immunization schedules resulted in dramatic declines in disease burden but may also be changing the rotavirus genetic landscape and driving the emergence of new genotypes. We report genotype data of more than 16,000 rotavirus isolates from 40 countries participating in the Global Rotavirus Surveillance Network. Data from a convenience sample of children under five years of age hospitalized with acute watery diarrhea who tested positive for rotavirus were included. Country results were weighted by their estimated rotavirus disease burden to estimate regional genotype distributions. Globally, the most frequent genotypes identified after weighting were G1P[8] (31%), G1P[6] (8%) and G3P[8] (8%). Genotypes varied across WHO Regions and between countries that had and had not introduced rotavirus vaccine. G1P[8] was less frequent among African (36 vs 20%) and European (33 vs 8%) countries that had introduced rotavirus vaccines as compared to countries that had not introduced. Our results describe differences in the distribution of the most common rotavirus genotypes in children with diarrhea in low- and middle-income countries. G1P[8] was less frequent in countries that had introduced the rotavirus vaccine while different strains are emerging or re-emerging in different regions.
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Transcription of specific genes in bacteria under environmental stress is frequently initiated by extracytoplasmic function (ECF) σ factors. ECFs σ factors harbour two conserved domains, σ2 and σ4, for transcription initiation by recognition of the promoter region and recruitment of RNA polymerase (RNAP). The crystal structure of Streptomyces tsukubaensis SigG1, an ECF56-family σ factor, was determined revealing σ2, σ4 and the additional carboxi-terminal domain SnoaL_2 tightly packed in a compact conformation. The structure of anti-sigma RsfG was also determined by X-ray crystallography and shows a rare ß-barrel fold. Analysis of the metal binding motifs inside the protein barrel are consistent with Fe(III) binding, which is in agreement with previous findings that the Streptomyces tsukubaensis ECF56 SigG1-RsfG system is involved in metal-ion homeostasis.
Assuntos
Fator sigma , Streptomyces , Fator sigma/genética , Fator sigma/química , Fator sigma/metabolismo , Proteínas de Bactérias/química , Compostos Férricos , Modelos Moleculares , Streptomyces/genética , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/química , Regulação Bacteriana da Expressão GênicaRESUMO
BACKGROUND: Few studies have focused on microbial diversity in indoor environments of ships, as well as the role of the microbiome and its ecological interconnections. In this study, we investigated the microbiome and virome present on the internal surfaces of a polar ship in different stages (beginning, during, and at the end) of the Brazilian Antarctic expedition in order to evaluate abundance of microorganisms in different periods. OBJECTIVES AND METHODS: We used shotgun metagenomic analysis on pooled samples from sampling surfaces in the ship's interior to track the microbial diversity. FINDINGS: Considering the total fraction of the microbiome, the relative abundance of bacteria, eukaryotes, viruses, and archaea was 83.7%, 16.2%, 0.04%, and 0.002%, respectively. Proteobacteria was the most abundant bacterial phyla, followed by Firmicutes, Actinobacteria, and Bacteroidetes. Concerning the virome, the greatest richness of viral species was identified during the middle of the trip, including ten viral families after de novo assembly: Autographiviridae, Chrysoviridae, Genomoviridae, Herelleviridae, Myoviridae, Partitiviridae, Podoviridae, Potyviridae, Siphoviridae, and Virgaviridae. MAIN CONCLUSIONS: This study contributed to the knowledge of microbial diversity in naval transportation facilities, and variations in the abundance of microorganisms probably occurred due to factors such as the number of passengers and activities on the ship.
Assuntos
Microbiota , Viroma , Humanos , Navios , Regiões Antárticas , Archaea/genéticaRESUMO
Selenium uptake and its content in soybean grains are affected by Se application methods. This study evaluated the impact of Se foliar application combined with a multi-nutrient fertilizer (MNF) on soybean, establishing a Se threshold to better understand the relationship between Se content in grains and yield of two genotypes (58I60 Lança and M5917). Two trials were conducted in a 4 × 2 factorial design: four Se rates (0, 10, 40, 80 g Se ha-1) and two methods of foliar Se application (Se combined or not with MNF). Foliar fertilizers were applied twice, at phenological stages of beginning of pod development and grain filling. Grain yield increased with the application of MNF, yet Se rates increased Se contents linearly up to 80 g Se ha-1, regardless of the use of MNF. Lança and M5917 genotypes had grain Se critical thresholds of 1.0 and 3.0 mg kg-1, respectively. The application of Se favored higher contents of K, P, and S in grains of genotype Lança and higher contents of Mn and Fe in grains of genotype M5917. Our findings highlight the importance of addressing different Se fertilization strategies as well as genotypic variations when assessing the effects of Se on soybean yield and grain quality.
RESUMO
AIMS: The aim of this study was to investigate the antibacterial and antibiofilm potential of cordiaquinones B, E, L, N, and O against different Staphylococci strains, in addition to analyzing in silico the observed effect. METHODS AND RESULTS: The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined according to CLSI guidelines. The inhibition of biofilm formation was investigated at sub-MICs. Atomic force microscopy (AFM) and density functional theory method were performed. The tested strains of Staphylococcus spp. were susceptible to cordiaquinones B, E, and L, among which cordiaquinone B exerted a bactericidal effect, confirmed by a bacterial growth curve study, against Staphylococcus saprophyticus. Cordiaquinones B and E showed lowest MBC values against S. saprophyticus. AFM revealed that cordiaquinone L reduced the mean cell size of S. saprophyticus. Cordiaquinones B and E inhibited the biofilm formation ability of S. aureus by â¼90%. The in silico analysis suggested that the antimicrobial activity of cordiaquinones is driven by their electron donation capability. CONCLUSIONS: Cordiaquinones inhibit the growth and biofilm formation (virulence factor) of both methicillin-sensitive and methicillin-resistant Staphylococci strains, indicating their antimicrobial potential.
Assuntos
Antibacterianos , Biofilmes , Staphylococcus aureus Resistente à Meticilina , Naftoquinonas , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Naftoquinonas/farmacologia , Antibacterianos/farmacologia , Simulação por Computador , Testes de Sensibilidade Microbiana , Cordia/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Viabilidade Microbiana/efeitos dos fármacosRESUMO
The introduction of rotavirus A (RVA) vaccines has considerably reduced the RVA-associated mortality among children under 5 years of age worldwide. The ability of RVA to reassort gives rise to different combinations of surface proteins G (glycoprotein, VP7) and P (protease sensitive, VP4) RVA types infecting children. During the epidemiological surveillance of RVA in the Northwest Amazon region, an unusual rotavirus genotype G6P[8] was detected in feces of a 2-year-old child with acute gastroenteritis (AGE) that had been vaccinated with one dose of Rotarix® (RV1). The G6P[8] sample had a DS-1-like constellation with a Wa-like VP3 gene mono-reassortment similar to equine-like G3P[8] that has been frequently detected in Brazil previously. The results presented here reinforce the evolutionary dynamics of RVA and the importance of constant molecular surveillance.