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Entamoeba histolytica, an intestinal parasite of global significance, poses substantial health risks with its associated high morbidity and mortality rates. Despite the current repertoire of molecular tools for the study of gene function in, the regulatory mechanisms governing its pathogenicity remain largely unexplored. This knowledge gap underscores the need to elucidate key genetic determinants orchestrating cellular functions critical to its virulence. Previously, our group generated an avirulent strain, termed UG10, with the same genetic background as the HM1:IMSS strain. UG10 strain, despite showing normal expression levels of well-known virulence factors, was unable to perform in-vitro and in-vivo activities related to amoebic virulence. In this study, we aimed to uncover the genome-wide modifications that rendered the avirulent phenotype of the UG10 strain through whole-genome sequencing. As a complementary approach, we conducted Methylated DNA Immunoprecipitation coupled with sequencing (MeDIP-seq) analysis on both the highly virulent HM1:IMSS strain and the low-virulence UG10 strain to uncover the genome-wide methylation profile. These dual methodologies revealed two aspects of the UG10 avirulent strain. One is the random integration of fragments from the ribosomal gene cluster and tRNA genes, ranging from 120 to 400â¯bp; and secondly, a clear, enriched methylation profile in the coding and non-coding strand relative to the start codon sequence in genes encoding small GTPases, which is associated with the previously described avirulent phenotype. This study provides the foundation to explore other genetic and epigenetic regulatory circuitries in E. histolytica and novel targets to understand the pathogenic mechanism of this parasite.
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Pyrophosphatases (PPases) are enzymes that catalyze the hydrolysis of pyrophosphate (PPi), a byproduct of the synthesis and degradation of diverse biomolecules. The accumulation of PPi in the cell can result in cell death. Although the substrate is the same, there are variations in the catalysis and features of these enzymes. Two enzyme forms have been identified in bacteria: cytoplasmic or soluble pyrophosphatases and membrane-bound pyrophosphatases, which play major roles in cell bioenergetics. In eukaryotic cells, cytoplasmic enzymes are the predominant form of PPases (c-PPases), while membrane enzymes (m-PPases) are found only in protists and plants. The study of bacterial cytoplasmic and membrane-bound pyrophosphatases has slowed in recent years. These enzymes are central to cell metabolism and physiology since phospholipid and nucleic acid synthesis release important amounts of PPi that must be removed to allow biosynthesis to continue. In this review, two aims were pursued: first, to provide insight into the structural features of PPases known to date and that are well characterized, and to provide examples of enzymes with novel features. Second, the scientific community should continue studying these enzymes because they have many biotechnological applications. Additionally, in this review, we provide evidence that there are m-PPases present in fungi; to date, no examples have been characterized. Therefore, the diversity of PPase enzymes is still a fruitful field of research. Additionally, we focused on the roles of H+/Na+ pumps and m-PPases in cell bioenergetics. Finally, we provide some examples of the applications of these enzymes in molecular biology and biotechnology, especially in plants. This review is valuable for professionals in the biochemistry field of protein structure-function relationships and experts in other fields, such as chemistry, nanotechnology, and plant sciences.
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Bactérias , Pirofosfatase Inorgânica , Pirofosfatase Inorgânica/metabolismo , Pirofosfatase Inorgânica/química , Pirofosfatase Inorgânica/genética , Bactérias/enzimologia , Fungos/enzimologia , Difosfatos/metabolismo , Difosfatos/químicaRESUMO
Background and Objectives: Medical and public recognition of "long-COVID or post-COVID syndrome", as well as its impact on the quality of life (QoL), is required to better address the disease burden. Objectives: We aimed to describe the persistence of COVID-19 symptoms and QoL among patients at three and twelve months after their discharge from the hospital. Materials and Methods: We conducted an observational, prospective, and longitudinal analytic study from September 2021 to April 2022. To measure QoL, we used a validated version of the 36-item Short-Form Health Survey (SF-36). Results: We included 68 patients in the study. A total of 54 (79.4%) patients reported at least one persistent symptom at three months vs. 52 (76.4%) at twelve months (p = 0.804). Some persistent symptoms (myalgia, alopecia, and cough) decreased significantly at twelve months (50% vs. 30.9%, 29.4% vs. 13.2%, and 23.5% vs. 7.4%; respectively, p = 0.007); in contrast, other persistent symptoms (sleep-wake and memory disorders) were more frequent (5.9% vs. 32.4% and 4.4% vs. 20.6%; respectively, p = ≤0.001). Regarding QoL, a statistically significant improvement was observed in some scores over time, p = ≤0.037. At twelve months, dyspnea, myalgia, and depression were risk factors associated with a poor physical component summary (PCS), p = ≤0.027, whereas anxiety, depression, and fatigue were associated with a poor mental component summary (MCS), p = ≤0.015. Conclusion: As the proportion of persistent symptoms at twelve months is high, we suggest that patients must continue under long-term follow up to reclassify, diagnose, and treat new onset symptoms/diseases.
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COVID-19 , Alta do Paciente , Qualidade de Vida , Humanos , COVID-19/psicologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Longitudinais , Idoso , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda , Adulto , Mialgia , Fatores de Tempo , Tosse/psicologia , Alopecia/psicologiaRESUMO
Sporothrix schenckii is one of the etiological agents of sporotrichosis, a cutaneous and subcutaneous infection distributed worldwide. Like other medically relevant fungi, its cell wall is a molecular scaffold to display virulence factors, such as protective pigments, hydrolytic enzymes, and adhesins. Cell wall proteins with adhesive properties have been previously reported, but only a handful of them have been identified and characterized. One of them is Gp70, an abundant cell wall protein mainly found on the surface of yeast-like cells. Since the protein also has a role in the activity of 3-carboxy-cis,cis-muconate cyclase and its abundance is low in highly virulent strains, its role in the Sporothrix-host interaction remains unclear. Here, a set of GP70-silenced strains was generated, and the molecular and phenotypical characterization was performed. The results showed that mutants with high silencing levels showed a significant reduction in the adhesion to laminin and fibrinogen, enzyme activity, and defects in the cell wall composition, which included reduced mannose, rhamnose, and protein content, accompanied by an increment in ß-1,3-glucans levels. The cell wall N-linked glycan content was significantly reduced. These strains induced poor TNFα and IL-6 levels when interacting with human peripheral blood mononuclear cells in a dectin-1-, TLR2-, and TLR4-dependent stimulation. The IL-1ß and IL-10 levels were significantly higher and were stimulated via dectin-1. Phagocytosis and stimulation of neutrophil extracellular traps by human granulocytes were increased in highly GP70-silenced strains. Furthermore, these mutants showed virulence attenuation in the invertebrate model Galleria mellonella. Our results demonstrate that Gp70 is a versatile protein with adhesin properties, is responsible for the activity of 3-carboxy-cis,cis-muconate cyclase, and is relevant for the S. schenckii-host interaction.
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The Escherichia coli Keio mutant collection has been a tool for assessing the role of specific genes and determining their role in E. coli physiology and uncovering novel functions. In this work, specific mutants in the DNA repair pathways and oxidative stress response were evaluated to identify the primary targets of silver nanoparticles (NPs) and their mechanism of action. The results presented in this work suggest that NPs mainly target DNA via double-strand breaks and base modifications since the recA, uvrC, mutL, and nfo mutants rendered the most susceptible phenotype, rather than involving the oxidative stress response. Concomitantly, during the establishment of the control conditions for each mutant, the katG and sodA mutants showed a hypersensitive phenotype to mitomycin C, an alkylating agent. Thus, we propose that KatG catalase plays a key role as a cellular chaperone, as reported previously for the filamentous fungus Neurospora crassa, a large subunit catalase. The Keio collection mutants may also be a key tool for assessing the resistance mechanism to metallic NPs by using their potential to identify novel pathways involved in the resistance to NPs.
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Mammalian models, such as murine, are used widely in pathophysiological studies because they have a high degree of similarity in body temperature, metabolism, and immune response with humans. However, non-vertebrate animal models have emerged as alternative models to study the host-pathogen interaction with minimal ethical concerns. Galleria mellonella is an alternative model that has proved useful in studying the interaction of the host with either bacteria or fungi, performing drug testing, and assessing the immunological response to different microorganisms. The G. mellonella immune response includes cellular and humoral components with structural and functional similarities to the immune effectors found in higher vertebrates, such as humans. An important humoral effector stimulated during infections is apolipophorin III (apoLp-III), an opsonin characterized by its lipid and carbohydrate-binding properties that participate in lipid transport, as well as immunomodulatory activity. Despite some parameters, such as the measurement of phenoloxidase activity, melanin production, hemocytes counting, and expression of antimicrobial peptides genes are already used to assess the G. mellonella immune response to pathogens with different virulence degrees, the apoLp-III quantification remains to be a parameter to assess the immune response in this invertebrate. Here, we propose an immunological tool based on an enzyme-linked immunosorbent assay that allows apoLp-III quantification in the hemolymph of larvae challenged with pathogenic agents. We tested the system with hemolymph coming from larvae infected with Escherichia coli, Candida albicans, Sporothrix schenckii, Sporothrix globosa, and Sporothrix brasiliensis. The results revealed significantly higher concentrations of apoLp-III when each microbial species was inoculated, in comparison with untouched larvae, or inoculated with phosphate-buffered saline. We also demonstrated that the apoLp-III levels correlated with the strains' virulence, which was already reported. To our knowledge, this is one of the first attempts to quantify apoLp-III, using a quick and easy-to-use serological technique.
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Mariposas , Humanos , Animais , Camundongos , Apolipoproteínas/química , Larva , Interações Hospedeiro-Patógeno , Mamíferos/metabolismoRESUMO
OBJECTIVE: Inferior vena cava filters (VCFs) are a therapeutic resource for the treatment of patients with thromboembolic disease who have a contraindication to full-dose anticoagulation. In the present study, we report the retrieval rate and long-term mortality of patients receiving optional inferior VCFs and identify the predictors for retrieval and all-cause mortality during follow-up. METHODS: We conducted a retrospective cohort study of 739 consecutive recipients of optional inferior VCFs from January 2002 to December 2021 in two hospitals. Different clinical characteristics and procedure-related variables were included in the analysis. The all-cause mortality rate and retrieval rate and the predictive factors were evaluated using multivariate analysis. RESULTS: Of the 739 patients, 393 (53%) were women. The mean patient age was 69 ± 15 years. Of the patients, 67% presented with pulmonary thromboembolism and 43% with deep vein thrombosis (DVT). A contraindication to anticoagulation was present for nearly 90% of the patients, mainly (47%) related to the surgical procedure. In addition, 44% of the patients had active cancer. Follow-up data were available for 94% of the patients, with an average follow-up time of 6.08 ± 5.83 years. Long-term mortality was 53%. Cancer (odds ratio [OR], 3.60; 95% confidence interval [CI], 2.22-5.83), age (OR, 1.03; 95% CI, 1.08-1.42), and DVT (OR, 2.01; 95% CI, 1.08-1.42) were identified as independent predictors of mortality. The retrieval rate at follow-up was 33%. The predictors for retrieval included the indication of the filter related to a surgical procedure (OR, 4.85; 95% CI, 2.54-9.59), the absence of cancer (OR, 2.89; 95% CI, 1.45-5.75), and younger age (OR, 0.98; 95% CI, 0.97-0.99). CONCLUSIONS: High long-term mortality was observed. The predictors of mortality were cancer, older age, and DVT. One third of the filters implanted were retrieved. The predictors for retrieval were a contraindication to surgery-related anticoagulation, the absence of cancer, and younger age.
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Neoplasias , Embolia Pulmonar , Filtros de Veia Cava , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Retrospectivos , Filtros de Veia Cava/efeitos adversos , Embolia Pulmonar/prevenção & controle , Embolia Pulmonar/tratamento farmacológico , Anticoagulantes/efeitos adversos , Neoplasias/complicações , Veia Cava Inferior , Remoção de Dispositivo/efeitos adversos , Resultado do TratamentoRESUMO
It is now widely demonstrated that excessive salt consumption can cause various health problems, and meat products are among the foods most consumed with a high salt content. For that, the aim of this work was to assess the effects of the utilization of flours obtained from oyster mushrooms (Pleurotus ostreatus), button mushrooms (Agaricus bisporus), and portobello mushrooms (Agaricus brunnescen) as salt replacers on chemical, physicochemical, and sensory properties of beef burgers. The fat and protein content was not affected by the inclusion of mushroom flour, while the sodium content was reduced by 55-61% compared to the control sample. The control sample had the lowest values for cooking loss and shrinkage (12.29 and 18.69%, respectively) whilst the reformulated samples had higher values ranging between 16.08 and 18.88% for cooking loss, respectively, and between 19.55 and 28.25% for shrinkage, respectively. The reformulated samples showed higher lipid oxidation values (ranging from 0.18 and 0.20 mg malondialdehyde/kg sample) than the control sample. Sensorially, all parameters analyzed were not affected by the replacement of sodium chloride by the different mushroom flours. The use of flours obtained from different mushroom flours is a viable alternative to be used as sodium chloride replacers in the preparation of beef burgers.
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Sporotrichosis is a cutaneous mycosis that affects humans and animals and has a worldwide distribution. This infection is mainly caused by Sporothrix schenckii, Sporothrix brasiliensis, and Sporothrix globosa. Current research about anti-Sporothrix immunity has been mainly focused on S. schenckii and S. brasiliensis, using different types of human or animal immune cells. Granulocytes are a group of cells relevant for cytokine production, with the capacity for phagocytosis and the generation of neutrophil extracellular traps (NETs). Considering their importance, this study aimed to compare the capacity of human granulocytes to stimulate cytokines, uptake, and form NETs when interacting with different Sporothrix species. We found that conidia, germlings, and yeast-like cells from S. schenckii, S. brasiliensis, and S. globosa play an important role in the interaction with these immune cells, establishing morphology- and species-specific cytokine profiles. S. brasil-iensis tended to stimulate an anti-inflammatory cytokine profile, whilst the other two species had a proinflammatory one. S. globosa cells were the most phagocytosed cells, which occurred through a dectin-1-dependent mechanism, while the uptake of S. brasiliensis mainly occurred via TLR4 and CR3. Cell wall N-linked and O-linked glycans, along with ß-1,3-glucan, played a significant role in the interaction of these Sporothrix species with human granulocytes. Finally, this study indicates that conidia and yeast-like cells are capable of inducing NETs, with the latter being a better stimulant. To the best of our knowledge, this is the first study that reports the cytokine profiles produced by human granulocytes interacting with Sporothrix cells.
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The quality characteristics (physical, techno-functional, and chemical) of date fruits (at the tamar stage) of two cultivars ("Confitera", autochthonous and unknown vs. "Medjoul", widely distributed and well-known), grown in the Southeast of Spain (Elche palm grove) were evaluated in order to reinforce decisions aimed at organizing the production of fresh dates from Elche by selecting the most profitable cultivar. Morphologically, Confitera dates were longer and with higher pulp yield than Medjoul dates (4.58 cm vs. 3.88 cm, and 84% vs. 78%, respectively) (p < 0.05). Nutritionally, both dates are a good source of carbohydrates (total sugars (43-48%) and dietary fiber (20-22%)), with small amounts of fat and proteins. The main free sugars in dates from both cultivars were glucose and fructose (reducing sugars). The most abundant mineral found in both date fruits were K, followed by Ca or Mg (depending on the cultivar; Ca in Medjoul and Mg in Confitera). Confitera dates showed a higher total antioxidant activity than Medjoul, corresponding with their higher (p < 0.05) content in polyphenolic compounds, mainly flavonoids (catechin and epicatechin predominantly). Confitera dates should be promoted in this region not only for their contribution to sustainable agricultural development and biodiversity, but also for their higher overall quality.
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Sporotrichosis is known as a subacute or chronic infection, which is caused by thermodimorphic fungi of the genus Sporothrix. It is a cosmopolitan infection, which is more prevalent in tropical and subtropical regions and can affect both humans and other mammals. The main etiological agents causing this disease are Sporothrix schenckii, Sporothrix brasiliensis, and Sporothrix globosa, which have been recognized as members of the Sporothrix pathogenic clade. Within this clade, S. brasiliensis is considered the most virulent species and represents an important pathogen due to its distribution and prevalence in different regions of South America, such as Brazil, Argentina, Chile, and Paraguay, and Central American countries, such as Panama. In Brazil, S. brasiliensis has been of great concern due to the number of zoonotic cases that have been reported over the years. In this paper, a detailed review of the current literature on this pathogen and its different aspects will be carried out, including its genome, pathogen-host interaction, resistance mechanisms to antifungal drugs, and the caused zoonosis. Furthermore, we provide the prediction of some putative virulence factors encoded by the genome of this fungal species.
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There is worldwide concern about the constant increase in infections caused by Candida species that are multiresistant to antifungal drugs. The most common candidiasis is caused by Candida albicans, however, the species of the Candida haemulonii complex and Candida auris are emerging opportunistic pathogens, which isolation from clinical samples has significantly increased in the past years. The special interest in the study of these species lies in their ability to evade the action of antifungal drugs, such as amphotericin B, azoles, and echinocandins. In addition, the phenotypic changes of these species have given them the ability to easily adapt to environmental changes, including the host milieu and immunity. In this paper, a detailed review of the current literature on the C. haemulonii complex and C. auris is shown, analyzing aspects such as biology, immune response, putative virulence factors, infection, treatment, and the current strategies for diagnosis.
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Parasitic weeds are noxious plants that damage crops of economic relevance, especially in Mediterranean and African countries. The strategy of suicidal germination was proposed to deal with this plague by using seed germination inducers that work as a pre-emergence herbicide and reduce the parasitic seed load before sowing. N-Substituted phthalimides with a furanone ring were found to be efficient in inducing the germination of Phelipanche ramosa and Orobanche cumana, two of the most problematic parasitic weeds of crops. However, the solubility of these compounds in water is low. A strategy for enhancing their aqueous solubility is the synthesis of host-guest complexes with cyclodextrins. Three bioactive phthalimide-lactones (PL01, PL04, and PL07) were selected and studied to form complexes of increased water solubility with α-, ß-, HP-ß-, and γ-cyclodextrin. The complexes obtained by the coprecipitation method, with increased aqueous solubility (up to 3.8 times), were studied for their bioactivity and they showed similar or slightly higher bioactivity than free phthalimide-lactones, even without the addition of organic solvents. A theoretical study using semiempirical calculations of molecular models including a solvation system confirmed the physicochemical empirical results. These results demonstrated that cyclodextrins can be used to improve the physicochemical and biological properties of parasitic seed germination inducers.
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Ciclodextrinas , Plantas Daninhas , Humanos , Lactonas/química , Ftalimidas , AgriculturaRESUMO
Chitosan is the deacetylated form of chitin regarded as one of the most abundant polymers and due to its properties, both chitosan alone or in combination with bioactive substances for the production of biodegradable films and coatings is gaining attention in terms of applications in the food industry. To enhance the antimicrobial and antioxidant properties of chitosan, a vast variety of plant extracts have been incorporated to meet consumer demands for more environmentally friendly and synthetic preservative-free foods. This review provides knowledge about the antioxidant and antibacterial properties of chitosan films and coatings enriched with natural extracts as well as their applications in various food products and the effects they had on them. In a nutshell, it has been demonstrated that chitosan can act as a coating or packaging material with excellent antimicrobial and antioxidant properties in addition to its biodegradability, biocompatibility, and non-toxicity. However, further research should be carried out to widen the applications of bioactive chitosan coatings to more foods and industries as well was their industrial scale-up, thus helping to minimize the use of plastic materials.
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INTRODUCTION: Immunosuppressive treatments have improved graft and patient survival rates, but can increase the incidence of post-transplant infections. OBJECTIVES: To analyze data from kidney transplant patients and describe the pathogens responsible for the infections they experience. METHODS: Longitudinal, analytical, observational study of 103 patients who underwent kidney transplantation. The follow-up period was 5.07 ± 1.28 years. RESULTS: Overall mortality rate was 10.68% and graft loss rate was 14.56%. Regarding recipient risk of death, the Cox regression model showed a hazard ratio (HR) of 5.66 for positive bacterial cultures and 2.22 for positive extended-spectrum beta-lactamase (ESBL)-producing strains; as for graft loss, HR was 4.59 in those with positive bacterial cultures and 4.25 in those who were positive for ESBL-producing strains. CONCLUSIONS: Significant death risk was found in kidney transplant recipients with positive bacterial cultures and an increased risk of graft loss in those with positive bacterial cultures and in those who were positive for ESBL-producing Enterobacteriaceae isolates. The rate of ESBL-producing Enterobacteriaceae is high, and stricter strategies are therefore necessary to control the use of antibiotics.
INTRODUCCIÓN: Los tratamientos inmunosupresores han mejorado las tasas de supervivencia del injerto y del paciente, pero pueden incrementar las infecciones postrasplante. OBJETIVOS: Analizar los datos de pacientes con trasplante renal y describir las bacterias responsables de las infecciones que presentan. MÉTODOS: Estudio observacional, longitudinal y analítico de 103 pacientes sometidos a trasplante renal. El periodo de seguimiento fue de 5.07 ± 1.28 años. RESULTADOS: La tasa de mortalidad fue de 10.68 % y la de pérdida del injerto de 14.56 %. Respecto al riesgo de muerte del receptor, el modelo de regresión de Cox mostró un cociente de riesgo (HR, hazard ratio) de 5.66 en los pacientes con cultivo bacteriano positivo y de 2.22 en aquellos con cepas productoras de betalactamasas de espectro extendido (BLEE); en cuanto a la pérdida del injerto, el HR fue de 4.59 en quienes tuvieron cultivo bacteriano positivo y de 4.25 en aquellos con cepas productoras de BLEE. CONCLUSIONES: Se encontró riesgo significativo de muerte en receptores de trasplante renal con cultivo bacteriano positivo y mayor riesgo de pérdida del injerto en aquellos con cultivo bacteriano positivo y aislamiento de cepas productoras de BLEE. La tasa de enterobacterias productoras de BLEE es alta, por ello son necesarias estrategias más estrictas para controlar del uso de antibióticos.
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Infecções por Enterobacteriaceae , Transplante de Rim , Humanos , Infecções por Enterobacteriaceae/etiologia , Infecções por Enterobacteriaceae/microbiologia , Transplante de Rim/efeitos adversos , México/epidemiologia , Enterobacteriaceae , Antibacterianos/uso terapêutico , beta-LactamasesRESUMO
The aim of this work was to obtain chitosan nanoparticles (<1000 nm) with chincho (Tagetes elliptica Sp.) essential oil (CEO-CSNPs) using the ionic gelation method. A Box−Behnken design (BBD) was applied, using chitosan solution (CS) pH (4.0, 4.4, 4.8); the mass ratio of CS/CEO (1:0.7, 1:0.85, 1:1.0) and the mass ratio of CS/CS-tripolyphosphate (1:0.46, 1:0.58, 1:0.7) as independent variables. The formulation-dependent variables, encapsulation efficiency (EE) and loading capacity (LC) of the CEO-CSNPs were evaluated. BBD determined that optimal conditions for CEO-CSNPs were pH: 4.4, CS/CEO mass ratio 1:0.7 and CS/TPP mass ratio 1:0.46. Once the optimization was defined, particle size (PS), zeta potential (ZP), polydispersity index (PDI), CEO-CSNPs morphological studies, in vitro CEO release, and antibacterial activity were determined. The CEO-CSNPs showed an EE of 52.64% and a LC of 11.56%, with a diameter of 458.5 nm, with a ZP of 23.30mV, and a PDI of 0.418. The SEM studies showed that the nanoparticles were rounded and had uniform shapes. In addition, CEO-CSNPs showed a minimum inhibitory concentration against Staphylococcus aureus, Salmonella infantis and Escherichia coli of 5.29, 10.57 and 10.57 µg/mL, respectively. These results could be very useful for the stabilization of chincho essential oil for food industry purposes. However, several studies about the release, as well as interaction with food matrices, will be necessary.
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Resumen Introducción: Los tratamientos inmunosupresores han mejorado las tasas de supervivencia del injerto y del paciente, pero pueden incrementar las infecciones postrasplante. Objetivos: Analizar los datos de pacientes con trasplante renal y describir las bacterias responsables de las infecciones que presentan. Métodos: Estudio observacional, longitudinal y analítico de 103 pacientes sometidos a trasplante renal. El periodo de seguimiento fue de 5.07 ± 1.28 años. Resultados: La tasa de mortalidad fue de 10.68 % y la de pérdida del injerto de 14.56 %. Respecto al riesgo de muerte del receptor, el modelo de regresión de Cox mostró un cociente de riesgo (HR, hazard ratio) de 5.66 en los pacientes con cultivo bacteriano positivo y de 2.22 en aquellos con cepas productoras de betalactamasas de espectro extendido (BLEE); en cuanto a la pérdida del injerto, el HR fue de 4.59 en quienes tuvieron cultivo bacteriano positivo y de 4.25 en aquellos con cepas productoras de BLEE. Conclusiones: Se encontró riesgo significativo de muerte en receptores de trasplante renal con cultivo bacteriano positivo y mayor riesgo de pérdida del injerto en aquellos con cultivo bacteriano positivo y aislamiento de cepas productoras de BLEE. La tasa de enterobacterias productoras de BLEE es alta, por ello son necesarias estrategias más estrictas para controlar del uso de antibióticos.
Abstract Introduction: Immunosuppressive treatments have improved graft and patient survival rates, but can increase the incidence of post-transplant infections. Objectives: To analyze data from kidney transplant patients and describe the pathogens responsible for the infections they experience. Methods: Longitudinal, analytical, observational study of 103 patients who underwent kidney transplantation. The follow-up period was 5.07 ± 1.28 years. Results: Overall mortality rate was 10.68% and graft loss rate was 14.56%. Regarding recipient risk of death, the Cox regression model showed a hazard ratio (HR) of 5.66 for positive bacterial cultures and 2.22 for positive extended-spectrum beta-lactamase (ESBL)-producing strains; as for graft loss, HR was 4.59 in those with positive bacterial cultures and 4.25 in those who were positive for ESBL-producing strains Conclusions: Significant death risk was found in kidney transplant recipients with positive bacterial cultures and an increased risk of graft loss in those with positive bacterial cultures and in those who were positive for ESBL-producing Enterobacteriaceae isolates. The rate of ESBL-producing Enterobacteriaceae is high, and stricter strategies are therefore necessary to control the use of antibiotics.
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In the work described here, a number of sesquiterpenes and benzoxazinoids from natural sources, along with their easily accessible derivatives, were evaluated against the main protease, RNA replicase and spike glycoprotein of SARS-CoV-2 by molecular docking. These natural products and their derivatives have previously shown remarkable antiviral activities. The most relevant compounds were the 4-fluoro derivatives of santamarine, reynosin and 2-amino-3H-phenoxazin-3-one in terms of the docking score. Those compounds fulfill the Lipinski's rule, so they were selected for the analysis by molecular dynamics, and the kinetic stabilities of the complexes were assessed. The addition of the 4-fluorobenzoate fragment to the natural products enhances their potential against all of the proteins tested, and the complex stability after 50 ns validates the inhibition calculated. The derivatives prepared from reynosin and 2-amino-3H-phenoxazin-3-one are able to generate more hydrogen bonds with the Mpro, thus enhancing the stability of the protein-ligand and generating a long-term complex for inhibition. The 4-fluoro derivate of santamarine and reynosin shows to be really active against the spike protein, with the RMSD site fluctuation lower than 1.5 Å. Stabilization is mainly achieved by the hydrogen-bond interactions, and the stabilization is improved by the 4-fluorobenzoate fragment being added. Those compounds tested in silico reach as candidates from natural sources to fight this virus, and the results concluded that the addition of the 4-fluorobenzoate fragment to the natural products enhances their inhibition potential against the main protease, RNA replicase and spike protein of SARS-CoV-2.
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Produtos Biológicos , COVID-19 , Sesquiterpenos , Antivirais/química , Antivirais/farmacologia , Benzoatos , Benzoxazinas/farmacologia , Produtos Biológicos/farmacologia , Proteases 3C de Coronavírus , Humanos , Hidrogênio , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteases/farmacologia , RNA Polimerase Dependente de RNA , SARS-CoV-2 , Glicoproteína da Espícula de CoronavírusRESUMO
The aim of this study was to analyze the effect of pork backfat (PB) substitution in a meat burger with a gelled emulsion (GE) elaborated with maca flour, soybean oil, and chincho essential oil (CEO). Lipid profile (gas chromatographyGC), health indices, physicochemical properties (CIELAB color, pH, texture profileTPA), and cooking and sensory characteristics of meat burgers were analyzed. Five formulations were evaluated: control (BC) (80% beef meat and 20% PB); BSM (10% PB + 10% GE); BSMC0.25 (BSM + 0.25% CEO); BSMC0.5 (BSM + 0.5% CEO), and BSMC1.0 (BSM + 1.0% CEO). GE substitution in meat burgers provided a healthier lipid profile; the amount of SFA was reduced (p < 0.05), while PUFA content was significantly increased (p < 0.05). Furthermore, the use of GE resulted in healthier PUFA/SFA ratios and lower atherogenic and thrombogenic indices. The addition of GE increased moisture content and decreased fat and protein contents. Color parameters (L*, b*, and C*) decreased after cooking. Hardness (p < 0.05), cooking losses, and shrinkage changes decreased with GE addition. Lipid oxidation levels were significantly (p < 0.05) affected by GE substitution. Therefore, the substitution of PB by GE can be considered as an effective strategy to produce healthier meat burgers without negatively affecting their physicochemical and technological properties.
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Hallucinogenic fungi, mainly those from the Psilocybe genus, are being increasingly consumed even though there is no control on their culture conditions. Due to the therapeutic potential as antidepressants and anxiolytics of the alkaloids that they produce (psilocin and psilocybin), some form of control on their production would be highly recommended. Prior to identifying their optimal culture condition, a methodology that allows their study is required. Microwave-assisted extraction method (MAE) is a technique that has proven its efficiency to extract different compounds from solid matrices. For this reason, this study intends to optimize a MAE method to extract the alkaloids found in Psylocibe cubensis. A surface-response Box-Behnken design has been employed to optimize such extraction method and significantly reduce time and other resources in the extraction process. Based on the Box-Behnken design, 50 °C temperature, 60% methanol as extraction solvent, 0.6 g:10 mL sample mass:solvent ratio and 5 min extraction time, were established as optimal conditions. These mild conditions, combined with a rapid and efficient UHPLC analysis result in a practical and economical methodology for the extraction of psilocin and psilocybin from Psylocibe cubensis.