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Acute lung injury caused by severe malaria (SM) is triggered by a dysregulated immune response towards the infection with Plasmodium parasites. Postmortem analysis of human lungs shows diffuse alveolar damage (DAD), the presence of CD8 lymphocytes, neutrophils, and increased expression of Intercellular Adhesion Molecule 1 (ICAM-1). P. berghei ANKA (PbA) infection in C57BL/6 mice reproduces many SM features, including acute lung injury characterized by DAD, CD8+ T lymphocytes and neutrophils in the lung parenchyma, and tissular expression of proinflammatory cytokines and adhesion molecules, such as IFNγ, TNFα, ICAM, and VCAM. Since this is related to a dysregulated immune response, immunomodulatory agents are proposed to reduce the complications of SM. The monocyte locomotion inhibitory factor (MLIF) is an immunomodulatory pentapeptide isolated from axenic cultures of Entamoeba hystolitica. Thus, we evaluated if the MLIF intraperitoneal (i.p.) treatment prevented SM-induced acute lung injury. The peptide prevented SM without a parasiticidal effect, indicating that its protective effect was related to modifications in the immune response. Furthermore, peripheral CD8+ leukocytes and neutrophil proportions were higher in infected treated mice. However, the treatment prevented DAD, CD8+ cell infiltration into the pulmonary tissue and downregulated IFNγ. Moreover, VCAM-1 expression was abrogated. These results indicate that the MLIF treatment downregulated adhesion molecule expression, impeding cell migration and proinflammatory cytokine tissular production, preventing acute lung injury induced by SM. Our findings represent a potential novel strategy to avoid this complication in various events where a dysregulated immune response triggers lung injury.
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Lesão Pulmonar Aguda , Modelos Animais de Doenças , Malária , Plasmodium berghei , Animais , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/etiologia , Camundongos , Malária/imunologia , Plasmodium berghei/imunologia , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/metabolismo , Pulmão/imunologia , Pulmão/patologia , Humanos , Feminino , OligopeptídeosRESUMO
Ilama leaves are an important source of secondary metabolites with promising anticancer properties. Cancer is a disease that affects a great number of people worldwide. This work aimed to investigate the in vivo, in vitro and in silico anticancer properties of three acyclic terpenoids (geranylgeraniol, phytol and farnesyl acetate) isolated from petroleum ether extract of ilama leaves. Their cytotoxic activity against U-937 cells was assessed using flow cytometry to determine the type of cell death and production of reactive oxygen species (ROS). Also, a morphological analysis of the lymph nodes and a molecular docking study using three proteins related with cancer as targets, namely, Bcl-2, Mcl-1 and VEGFR-2, were performed. The flow cytometry and histomorphological analysis revealed that geranylgeraniol, phytol and farnesyl acetate induced the death of U-937 cells by late apoptosis and necrosis. Geranylgeraniol and phytol induced a significant increase in ROS production. The molecular docking studies showed that geranylgeraniol had more affinity for Bcl-2 and VEGFR-2. In the case of farnesyl acetate, it showed the best affinity for Mcl-1. This study provides information that supports the anticancer potential of geranylgeraniol, phytol and farnesyl acetate as compounds for the treatment of cancer, particularly with the potential to treat non-Hodgkin's lymphoma.
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Simulação de Acoplamento Molecular , Extratos Vegetais , Folhas de Planta , Plantas Medicinais , Espécies Reativas de Oxigênio , Humanos , Folhas de Planta/química , Plantas Medicinais/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , México , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Animais , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Simulação por Computador , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Células U937RESUMO
Introducción: Las enfermedades cardiovasculares representan una causa importante de morbilidad y mortalidad durante la gestación, entre las que se destaca la miocardiopatía, que cursa como un síndrome de insuficiencia cardíaca. Objetivo: Caracterizar a pacientes con miocardiopatía periparto según variables clínicas y epidemiológicas de interés para la investigación. Métodos: Se realizó un estudio descriptivo y transversal de las 18 pacientes con diagnóstico de miocardiopatía periparto, asistidas en el Hospital General Docente Dr. Juan Bruno Zayas Alfonso de Santiago de Cuba en el período comprendido desde octubre de 2015 hasta diciembre de 2022. Resultados: En la serie predominaron las pacientes mayores de 35 años de edad (edad promedio de 32,6 años), además de la descendencia africana (50,0 %), la hipertensión arterial crónica (44,4 %) y la multiparidad (8,9 %) como factores de riesgo y la insuficiencia del ventrículo izquierdo como manifestación clínica. La fracción de eyección de dicho ventrículo estuvo regularmente disminuida y la respuesta al tratamiento farmacológico fue satisfactoria en el total de la muestra. Conclusiones: La miocardiopatía en el periparto es de baja incidencia en este centro; sin embargo, por la gravedad que representa, se impone el diagnóstico temprano y la intervención del personal especializado para evitar complicaciones.
Introduction: Cardiovascular diseases represent an important cause of morbidity and mortality during pregnancy, cardiomyopathy is notable as a syndrome of heart failure. Objective: To characterize patients with peripartum cardiomyopathy according to clinical and epidemiological variables of interest for the investigation. Methods: A descriptive and cross-sectional study of 18 patients with diagnosis of peripartum cardiomyopathy was carried out. They were assisted at Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba from October, 2015 to December, 2022. Results: In the series there was a prevalence of patients over 35 years (32.6 average age), besides African descendant (50.0 %), chronic hypertension (44.4 %) and multiparity (8.9 %) as risk factors and the left ventricle failure as clinical manifestation. The ejection fraction of this ventricle was regularly diminished and the pharmacological treatment response was satisfactory in all the sample. Conclusions: Peripartum cardiomyopathy is of low incidence in this center; however, due to its seriousness, the early diagnosis and the specialized staff intervention are necessary to avoid complications.
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In this work, we perform experimental and numerical investigations on the dynamics of camphor-infused discs, well-established as active particles in their behavior. Our analysis focuses on examining the individual dynamics of these discs within a confined circular domain, revealing that they exhibit characteristics akin to active chiral particles. To characterize this behavior effectively, we introduce a methodology for estimating key model parameter values from our experiments, including linear velocity, angular velocity, and angular noise intensity. To validate our findings, we compare our experimental results with numerical simulations of the model. Our results demonstrate a striking phenomenon associated with camphor-infused discs: a pronounced accumulation of particles along the boundary. This intriguing observation suggests the occurrence of an attractive interaction between the active particles and the boundary, resulting in a kind of adsorption effect. The latter results in the confinement of the camphor disc along the Petri dish wall, which we refer to as sliding dynamics. We empirically determine the velocity of the particle along the Petri dish wall as well as its fluctuations, properties whose behavior notably deviates from the bulk dynamics.
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Resumen A pesar de la alta diversidad de epífitas vasculares (EV) reportadas en Perú, no existe un listado actualizado que esté acorde con las nuevas delimitaciones taxonómicas y los nuevos conceptos de epífitas. En este trabajo actualizamos el listado de EV de Perú, a partir de una búsqueda bibliográfica y visitas a herbarios locales. Se actualizaron los nombres de las especies según World Flora Online, se confirmó su presencia en la EpiList, su distribución altitudinal y por departamento, su categoría de riesgo y endemismo; y finalmente, se estimó el coeficiente epífito. Encontramos 2462 especies, pertenecientes a 18 órdenes, 25 familias y 249 géneros. Las familias con mayor riqueza fueron Orchidaceae (1606), Bromeliaceae (201) y Piperaceae (139 spp.); el 85 % de las especies estaban en la EpiList (2088 spp.). El departamento con mayor riqueza fue Amazonas (709) y los de menor fueron Ica y Tacna (2 spp.). El rango altitudinal con mayor riqueza se ubica entre los 1501 - 2000 m (649); 689 especies son endémicas y 220 se encuentran en alguna categoría de riesgo; el cociente epífito es de 13.12. Esta actualización representa un incremento aproximado del 40%, lo que posiciona a Perú como el tercer país con mayor diversidad de EV. Se obtuvo un listado más completo y acorde con el concepto de epifitismo; con lo que se hace evidente la necesidad de incluir 384 especies a la EpiList, lo que ayudaría a complementar el listado global de EV en el mundo.
Abstract Despite the high diversity of vascular epiphytes (VE) reported in Peru, there is no updated checklist that is in line with the new taxonomic delimitations and the new concepts of epiphytes. In this study, we update the list of VE in Peru, based on a bibliographic search and visits to local herbaria. Species names were updated according to the World Flora Online, their presence in the EpiList was confirmed, as well as their altitudinal distribution and distribution by department, risk category, and endemism. Finally, the epiphyte coefficient was estimated. We found 2462 species, belonging to 18 orders, 25 families, and 249 genera. The families with the highest richness were Orchidaceae (1606), Bromeliaceae (201), and Piperaceae (139 spp.); 85% of the species were in the EpiList (2088 spp.). The department with the highest richness was Amazonas (709) and the lowest were Ica and Tacna (2 spp.). The altitudinal range with the highest richness is between 1501 - 2000 m (649); 689 species are endemic and 220 are in some risk category; the epiphyte quotient is 13.12. This update represents an approximate 40% increase, positioning Peru as the third country with the highest VE diversity. A more comprehensive list was obtained, in line with the concept of epiphytism, highlighting the need to include 384 species in the EpiList, which would help complement the global list of VE worldwide.
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Patients with hypoplastic left heart syndrome (HLHS) with intact atrial septum have an increased mortality rate. This presentation occurs in 6% to 10% of cases. We present a patient with fetal diagnosis of HLHS with restrictive atrial septum. We performed a cesarean section at 37 weeks of gestation, and under ex utero intrapartum treatment proceeded with a median sternotomy and transatrial stenting for left atrial decompression due to findings of intact atrial septum on the fetal echocardiogram performed during the procedure. Subsequently, the patient underwent hybrid stage I palliation followed by a comprehensive stage II procedure at five months of age, but unfortunately died from postoperative complications.
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Septo Interatrial , Síndrome do Coração Esquerdo Hipoplásico , Humanos , Gravidez , Feminino , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Cesárea , Átrios do Coração/cirurgia , Diagnóstico Pré-Natal , Resultado do Tratamento , Estudos RetrospectivosRESUMO
OBJECTIVE: The COVID-19 pandemic has affected the mental health of populations around the world, but few longitudinal studies of its impact on suicidal thoughts and behaviors have been published especially from low- and middle-income countries. METHODS: This is a prospective cohort study of 1,385 first-year students from 5 Universities in Mexico followed-up for 1 year. We report 1-year cumulative incidence of suicidal thoughts and behaviors before (September 19, 2019-March 29, 2020) and during the COVID-19 period (March 30, 2020-June 30, 2020), focusing on those in the COVID-19 period with risk conditions and positive coping strategies during the pandemic. RESULTS: There was an increase in the incidence of suicidal ideation during the COVID-19 period compared to the pre-COVID-19 period (RR 1.65, 95%CI 1.08-2.50). This increase was mostly found among students with heightened sense of vulnerability (RR 1.95), any poor coping behavior (RR 2.40) and a prior mental disorder (RR 2.41). While we found no evidence of an increased risk of suicidal planning or attempts, there was evidence that those without lifetime mental health disorders were at greater risk of suicidal plans than those with these disorders especially if they had poor coping strategies (RR 3.14). CONCLUSION: In the short term, how students deal with the pandemic, being at high risk and having poor coping behavior, increased the new occurrence of suicidal thoughts and behaviors. Studies with longer follow-up and interventions to reduce or enhance these behaviors are needed.HIGHLIGHTSSuicidal ideation increased during the COVID-19 periodThose with heightened sense of vulnerability and poor coping were more affectedStudies with longer follow-up are needed.
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COVID-19 , Ideação Suicida , Humanos , Tentativa de Suicídio/psicologia , Pandemias , Universidades , Estudos Prospectivos , México/epidemiologia , COVID-19/epidemiologia , Estudantes/psicologiaRESUMO
Background: Recent studies have suggested that metabolic syndrome (MS) encompasses a group of risk factors for developing chronic kidney disease (CKD). This work aimed to evaluate the antioxidant and anti-inflammatory effects of allicin in the kidney from an experimental model of MS. Methods: Male Wistar rats (220-250 g) were used, and three experimental groups (n = 6) were formed: control (C), metabolic syndrome (MS), and MS treated with allicin (16 mg/Kg/day, gastric gavage) (MS+A). MS was considered when an increase of 20% in at least three parameters (body weight, systolic blood pressure (SBP), fasting blood glucose (FBG), or dyslipidemia) was observed compared to the C group. After the MS diagnosis, allicin was administered for 30 days. Results: Before the treatment with allicin, the MS group showed more significant body weight gain, increased SBP, and FBG, glucose intolerance, and dyslipidemia. In addition, increased markers of kidney damage in urine and blood. Moreover, the MS increased oxidative stress and inflammation in the kidney compared to group C. The allicin treatment prevented further weight gain, reduced SBP, FBG, glucose intolerance, and dyslipidemia. Also, markers of kidney damage in urine and blood were decreased. Further, the oxidative stress and inflammation were decreased in the renal cortex of the MS+A compared to the MS group. Conclusion: Allicin exerts its beneficial effects on the metabolic syndrome by considerably reducing systemic and renal inflammation as well as the oxidative stress. These effects were mediated through the Nrf2 pathway. The results suggest allicin may be a therapeutic alternative for treating kidney injury induced by the metabolic syndrome risk factors.
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Intolerância à Glucose , Síndrome Metabólica , Insuficiência Renal Crônica , Ratos , Animais , Masculino , Antioxidantes/farmacologia , Síndrome Metabólica/tratamento farmacológico , Intolerância à Glucose/tratamento farmacológico , Ratos Wistar , Rim , Insuficiência Renal Crônica/tratamento farmacológico , Peso Corporal , Modelos Teóricos , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologiaRESUMO
Spinal cord injury is a traumatic lesion that causes a catastrophic condition in patients, resulting in neuronal deficit and loss of motor and sensory function. That loss is caused by secondary injury events following mechanical damage, which results in cell death. One of the most important events is inflammation, which activates molecules like proinflammatory cytokines (IL-1ß, IFN-γ, and TNF-α) that provoke a toxic environment, inhibiting axonal growth and exacerbating CNS damage. As there is no effective treatment, one of the developed therapies is neuroprotection of the tissue to preserve healthy tissue. Among the strategies that have been developed are the use of cell therapy, the use of peptides, and molecules or supplements that have been shown to favor an anti-inflammatory environment that helps to preserve tissue and cells at the site of injury, thus favoring axonal growth and improved locomotor function. In this review, we will explain some of these strategies used in different animal models of spinal cord injury, their activity as modulators of the immune system, and the benefits they have shown.
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Traumatismos da Medula Espinal , Animais , Humanos , Traumatismos da Medula Espinal/tratamento farmacológico , Inflamação/patologia , Neurônios/metabolismo , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo , Medula Espinal/metabolismo , Recuperação de Função Fisiológica/fisiologiaRESUMO
Intestinal diseases caused by protistan parasites of the genera Giardia (giardiasis), Entamoeba (amoebiasis), Cryptosporidium (cryptosporidiosis) and Blastocystis (blastocystosis) represent a major burden in human and animal populations worldwide due to the severity of diarrhea and/or inflammation in susceptible hosts. These pathogens interact with epithelial cells, promoting increased paracellular permeability and enterocyte cell death (mainly apoptosis), which precede physiological and immunological disorders. Some cell-surface-anchored and molecules secreted from these parasites function as virulence markers, of which peptide hydrolases, particularly cysteine proteases (CPs), are abundant and have versatile lytic activities. Upon secretion, CPs can affect host tissues and immune responses beyond the site of parasite colonization, thereby increasing the pathogens' virulence. The four intestinal protists considered here are known to secrete predominantly clan A (C1- and C2-type) CPs, some of which have been characterized. CPs of Giardia duodenalis (e.g., Giardipain-1) and Entamoeba histolytica (EhCPs 1-6 and EhCP112) degrade mucin and villin, cause damage to intercellular junction proteins, induce apoptosis in epithelial cells and degrade immunoglobulins, cytokines and defensins. In Cryptosporidium, five Cryptopains are encoded in its genome, but only Cryptopains 4 and 5 are likely secreted. In Blastocystis sp., a legumain-activated CP, called Blastopain-1, and legumain itself have been detected in the extracellular medium, and the former has similar adverse effects on epithelial integrity and enterocyte survival. Due to their different functions, these enzymes could represent novel drug targets. Indeed, some promising results with CP inhibitors, such as vinyl sulfones (K11777 and WRR605), the garlic derivative, allicin, and purified amoebic CPs have been obtained in experimental models, suggesting that these enzymes might be useful drug targets.
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Criptosporidiose , Cryptosporidium , Cisteína Proteases , Animais , Humanos , Virulência , Fatores de VirulênciaRESUMO
Importance: Guided internet-delivered cognitive behavioral therapy (i-CBT) is a low-cost way to address high unmet need for anxiety and depression treatment. Scalability could be increased if some patients were helped as much by self-guided i-CBT as guided i-CBT. Objective: To develop an individualized treatment rule using machine learning methods for guided i-CBT vs self-guided i-CBT based on a rich set of baseline predictors. Design, Setting, and Participants: This prespecified secondary analysis of an assessor-blinded, multisite randomized clinical trial of guided i-CBT, self-guided i-CBT, and treatment as usual included students in Colombia and Mexico who were seeking treatment for anxiety (defined as a 7-item Generalized Anxiety Disorder [GAD-7] score of ≥10) and/or depression (defined as a 9-item Patient Health Questionnaire [PHQ-9] score of ≥10). Study recruitment was from March 1 to October 26, 2021. Initial data analysis was conducted from May 23 to October 26, 2022. Interventions: Participants were randomized to a culturally adapted transdiagnostic i-CBT that was guided (n = 445), self-guided (n = 439), or treatment as usual (n = 435). Main Outcomes and Measures: Remission of anxiety (GAD-7 scores of ≤4) and depression (PHQ-9 scores of ≤4) 3 months after baseline. Results: The study included 1319 participants (mean [SD] age, 21.4 [3.2] years; 1038 women [78.7%]; 725 participants [55.0%] came from Mexico). A total of 1210 participants (91.7%) had significantly higher mean (SE) probabilities of joint remission of anxiety and depression with guided i-CBT (51.8% [3.0%]) than with self-guided i-CBT (37.8% [3.0%]; P = .003) or treatment as usual (40.0% [2.7%]; P = .001). The remaining 109 participants (8.3%) had low mean (SE) probabilities of joint remission of anxiety and depression across all groups (guided i-CBT: 24.5% [9.1%]; P = .007; self-guided i-CBT: 25.4% [8.8%]; P = .004; treatment as usual: 31.0% [9.4%]; P = .001). All participants with baseline anxiety had nonsignificantly higher mean (SE) probabilities of anxiety remission with guided i-CBT (62.7% [5.9%]) than the other 2 groups (self-guided i-CBT: 50.2% [6.2%]; P = .14; treatment as usual: 53.0% [6.0%]; P = .25). A total of 841 of 1177 participants (71.5%) with baseline depression had significantly higher mean (SE) probabilities of depression remission with guided i-CBT (61.5% [3.6%]) than the other 2 groups (self-guided i-CBT: 44.3% [3.7%]; P = .001; treatment as usual: 41.8% [3.2%]; P < .001). The other 336 participants (28.5%) with baseline depression had nonsignificantly higher mean (SE) probabilities of depression remission with self-guided i-CBT (54.4% [6.0%]) than guided i-CBT (39.8% [5.4%]; P = .07). Conclusions and Relevance: Guided i-CBT yielded the highest probabilities of remission of anxiety and depression for most participants; however, these differences were nonsignificant for anxiety. Some participants had the highest probabilities of remission of depression with self-guided i-CBT. Information about this variation could be used to optimize allocation of guided and self-guided i-CBT in resource-constrained settings. Trial Registration: ClinicalTrials.gov Identifier: NCT04780542.
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Terapia Cognitivo-Comportamental , Depressão , Humanos , Feminino , Adulto Jovem , Adulto , Depressão/terapia , Universidades , Ansiedade/terapia , Transtornos de Ansiedade/terapia , Transtornos de Ansiedade/psicologia , Terapia Cognitivo-Comportamental/métodos , Resultado do Tratamento , InternetRESUMO
We seek to evaluate whether Internet Gaming Disorder (IGD) among university students in Mexico during their first year at university predicts a long list of mental disorders a year later, controlling for baseline mental health disorders as well as demographics. This is a prospective cohort study with a one-year follow-up period conducted during the 2018-2019 academic year and followed up during the 2019-2020 academic year at six Mexican universities. Participants were first-year university students (n = 1741) who reported symptoms compatible with an IGD diagnosis at entry (baseline). Outcomes are seven mental disorders (mania, hypomania, and major depressive episodes; generalized anxiety disorder and panic disorder; alcohol use disorder and drug use disorder), and three groups of mental disorders (mood, anxiety, and substance use disorders) at the end of the one-year follow-up. Fully adjusted models, that included baseline controls for groups of mental disorders, rendered all associations null. The association between baseline IGD and all disorders and groups of disorders at follow-up was close to one, suggesting a lack of longitudinal impact of IGD on mental disorders. Conflicting results from available longitudinal studies on the role of IGD in the development of mental disorders warrant further research.
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Comportamento Aditivo , Transtorno Depressivo Maior , Transtornos Relacionados ao Uso de Substâncias , Jogos de Vídeo , Humanos , Seguimentos , Universidades , Estudos Prospectivos , Transtorno de Adição à Internet , Comportamento Aditivo/psicologia , Ansiedade , Transtornos de Ansiedade , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Mania , Jogos de Vídeo/psicologia , Estudantes , InternetRESUMO
BACKGROUND AND OBJECTIVES: Internet gaming disorder (IGD) is associated with health, social, and academic problems but whether these are consequences of the disorder rather than precursors or correlates is unclear. We aimed to evaluate whether IGD in the 1st year of university predicts health, academic and social problems 1 year later, controlling for baseline health, academic and social problems, demographics, and mental health symptoms. METHODS: In a prospective cohort study, 1741 university students completed both a baseline online survey in their 1st year and a follow-up survey 1 year later. Log-binomial models examined the strength of prospective associations between baseline predictor variables (IGD, baseline health, academic and social problems, sex, age, and mental health symptoms) and occurrence of health, academic and social problems at follow-up. RESULTS: When extensively adjusted by the corresponding outcome at baseline, any mental disorder symptoms, sex, and age, baseline IGD was associated only with severe school impairment and poor social life (risk ratio [RR] = 1.77; 95% confidence interval [CI] = 1.14-2.75, p = .011; RR = 1.22; 95% CI = 1.07-1.38, p = .002, respectively). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: University authorities and counselors should consider that incoming 1st-year students that meet criteria for IGD are likely to have increased academic and social impairments during their 1st year for which they may want to intervene. This study adds to the existing literature by longitudinally examining a greater array of negative outcomes of IGD than previously documented.
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Desempenho Acadêmico , Comportamento Aditivo , Jogos de Vídeo , Humanos , Estudos Longitudinais , Estudos Prospectivos , Transtorno de Adição à Internet , Jogos de Vídeo/psicologia , Comportamento Aditivo/psicologia , Estudantes , Nível de Saúde , InternetRESUMO
Several classical problems in symbolic dynamics concern the characterization of the simplex of measures of maximal entropy. For subshifts of finite type in higher dimensions, methods of statistical mechanics are ideal for dealing with these problems. R. Burton and J. Steif developed a strategy to construct examples of strongly irreducible subshifts of finite type admitting several measures of maximal entropy. This strategy exploits a correspondence between equilibrium statistical mechanics and symbolic dynamics-a correspondence which was later formalized by O. Häggström. In this paper, we revisit and discuss this correspondence with the aim of presenting a simplified version of it and present some applications of rigorous results concerning the Potts model and the six-vertex model to symbolic dynamics, illustrating in this way the possibilities of this correspondence.
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Currently, demand for functional foods is increasing in the public interest in order to improve life expectations and general health. Food matrices containing probiotic microorganisms and active compounds encapsulated into carrier agents are essential in this context. Encapsulation via the lyophilisation method is widely used because oxidation reactions that affect physicochemical and nutritional food properties are usually avoided. Encapsulated functional ingredients, such as quercetin and Bacillus clausii, using two carrier agents' matrices-I [inulin (IN), lactose (L) and maltodextrin (MX)] and II [arabic (A), guar (G), and xanthan (X) gums)]-are presented in this work. A D-optimal procedure involving 59 experiments was designed to evaluate each matrix's yield, viability, and antioxidant activity (AA). Matrix I (33.3 IN:33.3 L:33.3 MX) and matrix II (33.3 A:33.3 G:33.3 X) exhibited the best yield; viability of 9.7 log10 CFU/g and 9.73 log10 CFU/g was found in matrix I (using a ratio of 33.3 IN:33.3 L:33.3 MX) and matrix II (50 G:50 X), respectively. Results for the antioxidant capacity of matrix I (100 IN:0 L:0M X) and matrix II (0 A:50 G:50 X) were 58.75 and 55.54 (DPPH* scavenging activity (10 µg/mL)), respectively. Synergy between matrices I and II with use of 100IN:0L:OMX and 0A:50G:50X resulted in 55.4 log10 CFU/g viability values; the antioxidant capacity was 9. 52 (DPPH* scavenging activity (10 µg/mL). The present work proposes use of a carrier agent mixture to produce a functional ingredient with antioxidant and probiotic properties that exceed the minimum viability, 6.0 log10 CFU/g, recommended by the FAO/WHO (2002) to be probiotic, and that contributes to the recommended daily quercetin intake of 10-16 mg/day or inulin intake of 10-20 g/day and dietary fibre intake of 25-38 g per day.
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Dystrophin Dp71 is the most abundant product of the Duchenne muscular dystrophy gene in the nervous system, and mutations impairing its function have been associated with the neurodevelopmental symptoms present in a third of DMD patients. Dp71 is required for the clustering of neurotransmitter receptors and the neuronal differentiation of cultured cells; nonetheless, its precise role in neuronal cells remains to be poorly understood. In this study, we analyzed the effect of two pathogenic DMD gene point mutations on the Dp71 function in neurons. We engineered C272Y and E299del mutations to express GFP-tagged Dp71 protein variants in N1E-115 and SH-SY5Y neuronal cells. Unexpectedly, the ectopic expression of Dp71 mutants resulted in protein aggregation, which may be mechanistically caused by the effect of the mutations on Dp71 structure, as predicted by protein modeling and molecular dynamics simulations. Interestingly, Dp71 mutant variants acquired a dominant negative function that, in turn, dramatically impaired the distribution of different Dp71 protein partners, including ß-dystroglycan, nuclear lamins A/C and B1, the high-mobility group (HMG)-containing protein (BRAF35) and the BRAF35-family-member inhibitor of BRAF35 (iBRAF). Further analysis of Dp71 mutants provided evidence showing a role for Dp71 in modulating both heterochromatin marker H3K9me2 organization and the neuronal genes' expression, via its interaction with iBRAF and BRAF5.
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Distrofina , Neuroblastoma , Distroglicanas/genética , Distrofina/genética , Heterocromatina , Proteínas de Grupo de Alta Mobilidade/genética , Proteínas de Grupo de Alta Mobilidade/metabolismo , Humanos , Laminas/genética , Neurônios/metabolismo , Lâmina Nuclear/metabolismo , Mutação Puntual , Agregados Proteicos , Receptores de Neurotransmissores/genéticaRESUMO
This paper presents a structural equation model to determine the job satisfaction and occupational health impacts concerning organizational and physical ergonomics, using (as a study) objective unionized workers from the University of Sonora, South Campus, as an educational enterprise, during the SARS-CoV-2 pandemic. The above is a key element of an organizational sustainability framework. In fact, there exists a knowledge gap about the relationship between diverse ergonomic factors, job satisfaction, and occupational health, in the educational institution's context. The method used was a stratified sample of workers to which a job satisfaction-occupational health questionnaire was applied, consisting of 31 items with three-dimensional variables. As a result, the overall Cronbach's Alpha coefficient was determined, 0.9028, which is considered adequate to guarantee reliability (i.e., very high magnitude). Therefore, after the structural equation model, only 12 items presented a strong correlation, with a good model fit of 0.036 based on the root mean square error of approximation, 1.09 degrees of freedom for the chi-square, 0.9 for the goodness of fit index, and a confidence level of 95%. Organizational and physical factors have positive impacts on job satisfaction with factor loads of 0.37 and 0.53, respectively, and p-values of 0.016 and 0.000, respectively. The constructs related to occupational health that are considered less important by the workers were also determined, which would imply a mitigation strategy. The results contribute to the body of knowledge concerning the ergonomic dimensions mentioned and support organizational sustainability improvements in educational institutions and other sectors.
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COVID-19 , Saúde Ocupacional , COVID-19/epidemiologia , Estudos Transversais , Ergonomia , Humanos , Satisfação no Emprego , Pandemias , Reprodutibilidade dos Testes , SARS-CoV-2 , Inquéritos e Questionários , UniversidadesRESUMO
Giardia duodenalis causes giardiasis, a major diarrheal disease in humans worldwide whose treatment relies mainly on metronidazole (MTZ) and albendazole (ABZ). The emergence of ABZ resistance in this parasite has prompted studies to elucidate the molecular mechanisms underlying this phenomenon. G. duodenalis trophozoites convert ABZ into its sulfoxide (ABZSO) and sulfone (ABZSOO) forms, despite lacking canonical enzymes involved in these processes, such as cytochrome P450s (CYP450s) and flavin-containing monooxygenases (FMOs). This study aims to identify the enzyme responsible for ABZ metabolism and its role in ABZ resistance in G. duodenalis. We first determined that the iron-containing cofactor heme induces higher mRNA expression levels of flavohemoglobin (gFlHb) in Giardia trophozoites. Molecular docking analyses predict favorable interactions of gFlHb with ABZ, ABZSO and ABZSOO. Spectral analyses of recombinant gFlHb in the presence of ABZ, ABZSO and ABZSOO showed high affinities for each of these compounds with Kd values of 22.7, 19.1 and 23.8 nM respectively. ABZ and ABZSO enhanced gFlHb NADH oxidase activity (turnover number 14.5 min-1), whereas LC-MS/MS analyses of the reaction products showed that gFlHb slowly oxygenates ABZ into ABZSO at a much lower rate (turnover number 0.01 min-1). Further spectroscopic analyses showed that ABZ is indirectly oxidized to ABZSO by superoxide generated from the NADH oxidase activity of gFlHb. In a similar manner, the superoxide-generating enzyme xanthine oxidase was able to produce ABZSO in the presence of xanthine and ABZ. Interestingly, we find that gFlHb mRNA expression is lower in albendazole-resistant clones compared to those that are sensitive to this drug. Furthermore, all albendazole-resistant clones transfected to overexpress gFlHb displayed higher susceptibility to the drug than the parent clones. Collectively these findings indicate a role for gFlHb in ABZ conversion to its sulfoxide and that gFlHb down-regulation acts as a passive pharmacokinetic mechanism of resistance in this parasite.
Assuntos
Anti-Helmínticos , Giardia lamblia , Albendazol/química , Albendazol/farmacocinética , Animais , Anti-Helmínticos/farmacologia , Biotransformação , Cromatografia Líquida , Citocromos/metabolismo , Flavinas/metabolismo , Giardia lamblia/genética , Giardia lamblia/metabolismo , Heme/metabolismo , Humanos , Ferro , Metronidazol/farmacologia , Oxigenases de Função Mista/metabolismo , Simulação de Acoplamento Molecular , RNA Mensageiro/metabolismo , Sulfonas , Sulfóxidos/metabolismo , Superóxidos , Espectrometria de Massas em Tandem , Trofozoítos/metabolismo , Xantina Oxidase/metabolismo , XantinasRESUMO
Enolase, a multifunctional protein expressed by multiple pathogens activates plasminogen to promote proteolysis on components of the extracellular matrix, an important event in early host-pathogen interactions. A secreted form of enolase that is released upon the interaction of trophozoites with epithelial cells has been detected in the secretome of G. duodenalis. However, the role of enolase in the host-pathogen interactions remains largely unknown. In this work, the effects of G. duodenalis enolase (Gd-eno) on the epithelial cell model (IEC-6) were analyzed. Firstly, the coding sequence of Giardia enolase was cloned and the recombinant protein used to raise antibodies that were then used to define the localization and role of enolase in epithelial cell-trophozoite interactions. Gd-eno was detected in small cytoplasmic vesicles as well as at the surface and is enriched in the region of the ventral disk of Giardia trophozoites. Moreover, the blocking of the soluble monomeric form of the enzyme, which is secreted upon interaction with IEC-6 cells by the anti-rGd-eno antibodies, significantly inhibited trophozoite attachment to intestinal IEC-6 cell monolayers. Further, rGd-eno was able to bind human plasminogen (HsPlg) and enhanced plasmin activity in vitro when the trophozoites were incubated with the intrinsic plasminogen activators of epithelial cells. In IEC-6 cells, rGd-eno treatment induced a profuse cell damage characterized by copious vacuolization, intercellular separation and detachment from the substrate; this effect was inhibited by either anti-Gd-eno Abs or the plasmin inhibitor ϵ- aminocaproic acid. Lastly, we established that in epithelial cells rGd-eno treatment induced a necroptotic-like process mediated by tumor necrosis factor α (TNF-α) and the apoptosis inducing factor (AIF), but independent of caspase-3. All together, these results suggest that Giardia enolase is a secreted moonlighting protein that stimulates a necroptotic-like process in IEC-6 epithelial cells via plasminogen activation along to TNFα and AIF activities and must be considered as a virulence factor.
Assuntos
Giardia lamblia , Giardíase , Animais , Comunicação Celular , Giardia/metabolismo , Giardia lamblia/metabolismo , Humanos , Fosfopiruvato Hidratase/metabolismo , Plasminogênio/metabolismo , Trofozoítos/metabolismoRESUMO
Cardiovascular diseases (CVDs) are a group of diseases in which the common denominator is the affection of blood vessels, heart tissue, and heart rhythm. The genesis of CVD is complex and multifactorial; therefore, approaches are often based on multidisciplinary management and more than one drug is used to achieve the optimal control of risk factors (dyslipidemia, hypertension, hypertrophy, oxidative stress, endothelial dysfunction, inflammation). In this context, allicin, a sulfur compound naturally derived from garlic, has shown beneficial effects on several cardiovascular risk factors through the modulation of cellular mechanisms and signaling pathways. Effective pharmacological treatments for CVD or its risk factors have not been developed or are unknown in clinical practice. Thus, this work aimed to review the cellular mechanisms through which allicin exerts its therapeutic effects and to show why it could be a therapeutic option for the prevention or treatment of CVD and its risk factors.