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The management of water resources in hyper-arid coastal regions is a challenging task because proper information regarding groundwater recharge and water budget is needed for maintaining the hydraulic balance in optimal conditions, avoiding salinization and seawater intrusion. Thus, this article deals with the estimation of the hydraulic recharge and the study of the effects of salinization on the dynamics of major and trace elements in an alluvial aquifer located in the world's driest zone, the northern Atacama Desert. The result of stable water isotopes (δD and δ18O) and tritium (3H) indicated that groundwater in the area is not recent, whereas 14C results estimated a groundwater residence time ranging between 11,628 and 16,067 yBP. The estimation of the artificial recharge coming from the urban water-supply-system leaks and wastewater/river-water/groundwater infiltration during irrigation was about 19.84 hm3/year, which represents an annual negative water balance of 177 hm3/year for the aquifer. The groundwater salinization triggered by seawater intrusion (up to 32.6 %) has caused the enrichment of Li, Rb, Ca, Ba, and Sr in groundwater by cationic exchange, where the excess of aqueous Na is exchanged by these elements in the aquifer sediments. Other elements such as B, Se, Si, and Sb are enriched in groundwater by ionic strength and/or anionic exchange during salinization. The heightened B concentrations derived from the B-rich alluvial sediments were higher than the limit suggested by international guidelines, representing a risk to consumers. Vanadium seems to be unaffected by salinization, whereas Pb, Mo, As, U, and Zr did not show a clear behavior during saline intrusion. Finally, this article highlights the consequences of conducting improper water management in coastal hyper-arid regions with exacerbated agriculture.
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Research on medicinal plants is essential for their conservation, propagation, resistance to environmental stress, and domestication. The use of organic nutrition has been demonstrated to improve soil fertility and plant quality. It is also important to study the effects of the Basic Cation Saturation Ratio (BCSR) approach, which is a topic where there is currently controversy and limited scientific information. Evaluating the growth and yields of Agastache mexicana subsp. mexicana (Amm) in different environments is crucial for developing effective propagation and domestication strategies. This includes examining warm and subhumid environments with rain in summer in comparison to mild environments with summer rain. Significant differences were observed in the effects of cold, waterlogging, and heat stresses on the plant's biomass yield and the morphometric-quantitative modeling by means of isolines. The biomass yield was 56% higher in environment one compared to environment two, 19% higher in environment one with organic nutrition, and 48% higher in environment two with organic nutrition compared to using only BCSR nutrition. In the second harvesting cycle, the plants in environment one did not survive, while the plants in environment two managed to survive without needing additional nutrition. Statistical and mathematical analyses provided information about the population or sample. Additionally, further analysis using isolines as a new approach revealed new insights into understanding phenology and growth issues.
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RESUMEN Introducción . El consumo excesivo de sal (cloruro de sodio, NaCl) en la dieta conduce al desarrollo de hipertensión arterial (HTA) y daño de órgano blanco. Se sabe que los canales ClC-K1 y ClC-5 son reguladores esenciales del anión cloruro (Cl-), pero la contribución de este anión a los efectos deletéreos de la sal es aún desconocida. Objetivo . El objetivo de este trabajo fue evaluar la participación del Cl- en la respuesta inflamatoria y oxidativa renal y en el desarrollo de HTA. Material y métodos . Ratas Wistar macho se dividieron en cuatro grupos (n=8/grupo) y se alimentaron con diferentes dietas durante 3 semanas. control (grupo C); NaCl 8 % (grupo NaCl); dieta alta en Na+. citrato de sodio (Na3C6H5O7) 11,8 % (grupo Na); dieta alta en Cl-. cloruro de calcio (CaCl2) 3,80 %, cloruro de potasio (KCl) 3,06 % y cloruro de magnesio (MgCl2) 1,30 % (grupo Cl). Se determinó la presión arterial sistólica (PAS), función renal, marcadores de estrés oxidativo y de inflamación en corteza renal, y la expresion renal de los canales de cloruro ClC-K1 y ClC-5. Resultados . Se observó un aumento de la PAS, actividad de glutatión peroxidasa (GPx) y expresión renal de factor nuclear kappa B (NFkB) y receptor de angiotensina II tipo 1 (AT1R) en los grupos NaCl y Cl- (p<0,05). La producción de sustancias reactivas del ácido tiobarbitúrico (TBARS) aumentó en los grupos experimentales con respecto a C. La expresión de la proteína de Parkinson 7 (PARK7) disminuyó en el grupo Cl en comparación con C (p< 0,05). Los grupos NaCl y Cl- mostraron una mayor expresión de ClC-K1, mientras que ClC-5 se redujo en el grupo NaCl en comparación con C (p<0,05). Conclusión . El Cl- sería corresponsable, junto con el Na+, de desencadenar daño oxidativo e inflamatorio renal y aumentar la presión arterial; por ello se deduce la importancia de reducir la ingesta de ambos iones como medida preventiva no farmacológica para la prevención y control de la HTA. El rol de los canales ClC-K1 y ClC-5 como mediadores de este proceso queda aún por confirmarse.
ABSTRACT Background . Excessive consumption of salt (sodium chloride, NaCl) in the diet leads to the development of hypertension (HTN) and target organ damage. It is known that the ClC-K1 and ClC-5 channels are essential regulators of the chloride (Cl-) anion, but the contribution of this anion to salt-harmful effects remains unknown. Objective . The aim of this study was to evaluate the participation of Cl- in the renal inflammatory and oxidative response and in the development of HTN. Methods . Male Wistar rats were divided into four groups (n=8/group) and fed with different diets for 3 weeks. control (C group); NaCl 8% (NaCl group); high Na+ diet. sodium citrate (Na3C6H5O7) 11.8% (Na group); high Cl- diet. calcium chloride (CaCl2) 3.80%, potassium chloride (KCl) 3.06% and magnesium chloride (MgCl2) 1.30% (Cl group). Systolic blood pressure (SBP), renal function, oxidative stress and inflammation markers in the renal cortex, and renal expression of the chloride ClC-K1 and ClC-5 channels were assessed. Results . An increase in SBP, glutathione peroxidase (GPx) activity, and renal expression of nuclear factor kappa B (NFkB) and angiotensin II type 1 receptor (AT1R) were observed in the NaCl and Cl groups (p<0.05). The production of thiobarbituric acid reactive substances (TBARS) increased in the experimental groups compared with C. The expression of Parkinson disease protein 7 (PARK7) decreased in the Cl group compared with C (p< 0.05). The NaCl and Cl groups showed increased expression of ClC-K1, while ClC-5 was reduced in the NaCl group compared with C (p<0.05) Conclusion . Cl- would be co-responsible together with Na+ in triggering oxidative and inflammatory kidney damage and increasing blood pressure. This indicates the importance of reducing the intake of both ions as a non-pharmacological preventive measure for the prevention and control of HTN. The role of ClC-K1 and ClC-5 channels as mediators of this process remains to be confirmed.
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This study aims to evaluate the impact of liver fibrosis stages of chronic infection with hepatitis C virus (HCV) on the in vivo activity of organic cation transporters (hepatic OCT1 and renal OCT2) using metformin (MET) as a probe drug. Participants allocated in Group 1 (n = 15, mild to moderate liver fibrosis) or 2 (n = 13, advanced liver fibrosis and cirrhosis) received a single MET 50 mg oral dose before direct-acting antiviral (DAA) drug treatment (Phase 1) and 30 days after achieving sustained virologic response (Phase 2). OCT1/2 activity (MET AUC0-24) was found to be reduced by 25% when comparing the two groups in Phase 2 (ratio 0.75 (0.61-0.93), p < 0.05) but not in Phase 1 (ratio 0.81 (0.66-0.98), p > 0.05). When Phases 1 and 2 were compared, no changes were detected in both Groups 1 (ratio 1.10 (0.97-1.24), p > 0.05) and 2 (ratio 1.03 (0.94-1.12), p > 0.05). So, this study shows a reduction of approximately 25% in the in vivo activity of OCT1/2 in participants with advanced liver fibrosis and cirrhosis after achieving sustained virologic response and highlights that OCT1/2 in vivo activity depends on the liver fibrosis stage of chronic HCV infection.
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Type 2 diabetes mellitus (T2DM) is a major global health problem. Response to first-line therapy is variable. This is partially due to interindividual variability across those genes codifying transport, metabolising, and drug activation proteins involved in first-line pharmacological treatment. Single nucleotide polymorphisms (SNPs) of genes SLC22A1, SLC22A2 and SLC22A3 affect metformin therapeutic response in patients with T2DM patients. The present study investigated allelic and genotypic frequencies of organic cation (OCT)1, OCT2, and OCT3 polymorphisms among metformin-treated patients with type 2 diabetes mellitus (T2DM). It also reports the association between clinical and genetic variables with glycated haemoglobin (HbA1c) control in 59 patients with T2DM. Patients were genotyped through real-time PCR (TaqMan assays). Metformin plasmatic levels were determined by mass spectrometry. Neither the analysis of HbA1c control by SNPs in SLC22A1, SLC22A2 and SLC22A3, nor the dominant genotypic model analysis yielded statistical significance between genotypes in polymorphisms rs72552763 (P=0.467), rs622342 (P=0.221), rs316019 (P=0.220) and rs2076828 (P=0.215). HbA1c levels were different in rs72552763 [GAT/GAT, 6.0 (5.7-6.6), GAT/del=6.5 (6.2-9.0), del/del=6.5 (6.4-6.8); P=0.022] and rs622342 [A/A=6.0 (5.8-6.5), A/C=6.4 (6.1-7.7), C/C=6.8 (6.4-9.3); P=0.009] genotypes. The dominant genotypic model found the lowest HbA1c levels in GAT/GAT (P=0.005) and A/A (P=0.010), in rs72552763 (GAT/GAT vs. GAT/del + del/del) and rs622342 (A/A vs. A/C + CC), respectively. There was a significant correlation between HbA1c levels and metformin dosage amongst del allele carriers in rs72552763 (ß1=0.14, P<0.001, r2=0.387), as opposed to GAT/GAT in rs72552763. There were no differences between HbA1c values in the test set and those predicted by machine learning models employing a simple linear regression based on metformin dosage. Therefore, rs72552763 and rs622342 polymorphisms in SLC22A1 may affect metformin response determined by HbA1c levels in patients with T2DM. The del allele of SNP rs72552763 may serve as a metformin response biomarker.
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Platelets are the critical target for preventing and treating pathological thrombus formation. However, despite current antiplatelet therapy, cardiovascular mortality remains high, and cardiovascular events continue in prescribed patients. In this study, first results were obtained with ortho-carbonyl hydroquinones as antiplatelet agents; we found that linking triphenylphosphonium cation to a bicyclic ortho-carbonyl hydroquinone moiety by a short alkyl chain significantly improved their antiplatelet effect by affecting the mitochondrial functioning. The mechanism of action involves uncoupling OXPHOS, which leads to an increase in mitochondrial ROS production and a decrease in the mitochondrial membrane potential and OCR. This alteration disrupts the energy production by mitochondrial function necessary for the platelet activation process. These effects are responsive to the complete structure of the compounds and not to isolated parts of the compounds tested. The results obtained in this research can be used as the basis for developing new antiplatelet agents that target mitochondria.
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Plaquetas , Hidroquinonas , Potencial da Membrana Mitocondrial , Compostos Organofosforados , Inibidores da Agregação Plaquetária , Humanos , Plaquetas/metabolismo , Plaquetas/efeitos dos fármacos , Hidroquinonas/farmacologia , Hidroquinonas/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Compostos Organofosforados/farmacologia , Compostos Organofosforados/química , Fosforilação Oxidativa/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/química , Espécies Reativas de Oxigênio/metabolismoRESUMO
El proyecto de resignificación educativa busca la forma-ción permanente del docente que piensa en la educación como proceso, para transformar el espacio educativo tradicional en un espacio democrático y participativo, con proyectos cooperativos e interdisciplinarios. Duran-te seis meses se trabajó desde la Investigación Acción Educativa (iae) (Elliot, 1998), por lo que los temas del programa se establecieron de acuerdo con los intereses y necesidades de los profesores y directores de la escuela. La implementación se realizó con la comunidad edu-cativa de una institución rural de São Paulo, en la cual se desarrollaron talleres semanales alrededor de las preguntas: ¿Cuáles serían las propuestas de trabajo di-recto con los estudiantes?, ¿qué cambios afectarían las concepciones y prácticas pedagógicas de los maestros y las relaciones entre todos los miembros de la comuni-dad escolar (estudiantes, maestros, empleados, familia, etc.)? Con los 217 estudiantes, de 4 a 11 años de esta institución, se trabajaron guiones de estudio basados en sus intereses. Los resultados preliminares de estos proyectos han demostrado que es posible construir la educación para la ciudadanía y la conciencia ambiental a través de acciones que tengan sentido para la comu-nidad escolar
The Educational Resignification Project seeks the per-manent training of the teacher who thinks of education as a process, to transform the traditional educational space into a democratic and participatory space, with cooperative and interdisciplinary projects. Work was carried out for six months using the Educational Action Research-iae (Elliot, 1998); therefore, the topics of the program were established according to the interests and needs of the teachers and school directors. The implemen-tation was conducted with the educational community of a rural institution in São Paulo, where weekly workshops were developed around the questions: What would be the proposals for direct work with students? and What changes would affect pedagogical conceptions and practices of teachers and the relationships between all members of the school community (students, teachers, employees, family, etc.)? With the 217 students from 04 to 11 years old at this school, study scripts were developed based on their interests. The preliminary projects' results showed it is possible to build education for citizenship and environmental awareness through actions that make sense for the school community.
O Projeto de Ressignificação Educacional busca a for-mação permanente do professor que pensa a educação como um processo, para transformar o espaço educa-cional tradicional em um espaço democrático e partici-pativo, com projetos cooperativos e interdisciplinares. Trabalhamos por seis meses a partir da Pesquisa-Ação Educacional (pae) (Elliot, 1998), de modo que os te-mas do programa foram estabelecidos de acordo com os interesses e necessidades dos professores e direto-res escolares. A implementação foi realizada com a comunidade educativa de uma instituição rural de São Paulo, onde foram desenvolvidas oficinas semanais em torno das questões: "Quais seriam as propostas de tra-balho direto com os alunos?"; "Que mudanças afetariam as concepções e práticas pedagógicas dos professores e as relações entre todos os membros da comunidade escolar (alunos, professores, funcionários, família, etc.)?". Com os 217 alunos de 04 a 11 anos desta escola, foram trabalhados roteiros de estudo baseados em seus in-teresses. Os resultados preliminares desses projetos mostraram que é possível construir educação para a cidadania e consciência ambiental por meio de ações que façam sentido para a comunidade escolar.
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Educação em Saúde Ambiental , Participação da Comunidade , Conscientização PúblicaRESUMO
Antivenom therapy is a critical intervention for treating the more than 5.000.000 envenomation accidents that occur each year around the world. These immunotherapeutic drugs are mostly produced following techniques developed more than fifty years ago with minor changes. Aggregate content has been described as one of the main causes of early adverse effects after intravenous administration of antivenoms. In this work we propose the introduction of a final polishing step to traditional antivenom manufacturing processes aimed at lowering the aggregate content in the final product. The refinement step proposed in this work is based on the selective capture of immunoglobulin aggregates by a cation exchange monolithic stationary phase. We show that this media can effectively remove aggregates in the final product under isotonic ion-strength and mildly acidic conditions following a negative chromatography strategy, thus making it a useful technique for producing higher quality products.
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Antivenenos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Cromatografia , Administração Intravenosa , Cromatografia por Troca Iônica/métodosRESUMO
Human plasma is full of therapeutic proteins that can be used to treat several diseases, among these proteins are immunoglobulins. IgG is currently the most important blood product because it accounts for around 30% of the market, which was estimated at 20 billion dollars in 2016 and continues to grow. IgM has multiple functions, such as controlling infections, producing dendritic cells and controlling tissue homeostasis. Because of its pentameric structure, IgM can also bind to antigens with greater avidity than other immunoglobulins. However, there are no commercially available IgM concentrates. In this work we studied the purification of plasma-derived IgM using liquid chromatography techniques and resins that can be easily scaled up. In the first step, plasma was purified on a Sepharose 4FF gel-filtration column. The enriched IgM fraction called F2 was then used as sample for cation exchange resin purifications. Experiments were initially carried out on Hi-Trap SP FF with the undiluted F2, five times diluted F2 and ten times diluted F2. Then we scaled up the purification using a 23mL SP Sepharose FF column using F2 diluted 10 times as loading sample. Our results indicate that the best of sample volume was 100mL, which corresponds to 63mg of protein. At pH 6.0 36% of IgM was not adsorbed on the column and 50% was adsorbed. At pH 5.0 IgM was recovered only in the Elution fraction, but the recovery was very poor (38%). Finally we carry out a purification at pH 5.0 using NaCl gradient to elute the adsorbed proteins. Due to the low concentration of proteins in the collected fractions, it was only possible to observe by immunoturbidimetry that 37.3% of IgM eluted in the 300mM NaCl to 500mM NaCl gradient. In this fraction, polyacrylamide gels show that IgG and albumin were present. The results obtained were preliminary and did not yet allow comparison of purification using cation exchange resin with anion exchange resins.
O plasma humano está repleto de proteínas terapêuticas que podem ser utilizadas no tratamento de várias doenças, entre essas proteínas estão as imunoglobulinas. O IgG é atualmente o hemoderivado mais importante porque é responsável por cerca de 30% do mercado, que era estimado em 20 bilhões de dólares em 2016 e continua a crescer. IgM tem múltiplas funções, como controle de infecções, produção de células dendríticas e controle da homeostase dos tecidual. Por conta de sua estrutura pentamérica, o IgM também pode-se ligar a antígenos com maior avidez do que outras imunoglobulinas. Entretanto não existem concentrados de IgM disponíveis comercialmente. Neste trabalho estudamos a purificação de IgM derivada de plasma usando técnicas de cromatografia líquida e resinas que podem ser facilmente escalonadas. Na primeira etapa foi feita a purificação de plasma em uma coluna de gel-filtração Sepharose 4FF. A fração enriquecida de IgM F2 foi então usada como amostra de entrada para as purificações em resina de troca catiônica. Primeiramente foram feitos experimentos em Hi-Trap SP FF com a amostra sem diluir, diluída cinco e dez vezes. Em seguida escalonamos a purificação empregando uma coluna SP Sepharose FF de 23mL usando como amostra de entrada F2 diluída 10 vezes. Verificamos que o volume ideal de amostra aplicada era de 100mL que corresponde a 63mg de proteína de amostra. Verificamos que em pH 6,0 36% de IgM não é adsorvido na coluna e 50% é adsorvido. Em pH 5,0 IgM foi recuperado somente na fração de Eluição, porém a recuperação foi muito baixa (38%). O último passo foi realizar uma purificação em pH 5,0 usando gradiente de NaCl para eluição das proteínas adsorvidas. Devido a baixa concentração de proteínas nas frações recolhidas foi possível apenas observar por imunoturbidimetria que 37,3% de IgM elui no gradiente NaCl 300mM ao NaCl 500mM. Nessa fração os géis de poliacrilamida mostram que IgG e Albumina estão presentes. Os resultados obtidos são preliminares e ainda não permitem comparar a purificação em resina de troca catiônica com resina de troca aniônica.
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Yarrowia lipolytica is a dimorphic fungus used as a model organism to investigate diverse biotechnological and biological processes, such as cell differentiation, heterologous protein production, and bioremediation strategies. However, little is known about the biological processes responsible for cation concentration homeostasis. Metals play pivotal roles in critical biochemical processes, and some are toxic at unbalanced intracellular concentrations. Membrane transport proteins control intracellular cation concentrations. Analysis of the Y. lipolytica genome revealed a characteristic functional domain of the cation efflux protein family, i.e., YALI0F19734g, which encodes YALI0F19734p (a putative Yl-Dmct protein), which is related to divalent metal cation tolerance. We report the in silico analysis of the putative Yl-Dmct protein's characteristics and the phenotypic response to divalent cations (Ca2+, Cu2+, Fe2+, and Zn2+) in the presence of mutant strains, Δdmct and Rdmct, constructed by deletion and reinsertion of the DMCT gene, respectively. The absence of the Yl-Dmct protein induces cellular and growth rate changes, as well as dimorphism differences, when calcium, copper, iron, and zinc are added to the cultured medium. Interestingly, the parental and mutant strains were able to internalize the ions. Our results suggest that the protein encoded by the DMCT gene is involved in cell development and cation homeostasis in Y. lipolytica.
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BACKGROUND: Cisplatin appears to enter the cochlear cells through the organic cation transporter 2 (OCT2). There is recent evidence that multidrug and toxin extrusion protein 1 (MATE1) is involved in cisplatin-induced nephrotoxicity. Its presence and role in the ear are unknown. AIMS/OBJECTIVES: Evaluate the presence and localization of MATE1, and determine the localization of OCT2, in the cochlea. Evaluate cisplatin uptake with regard to MATE1 and OCT2 expression. MATERIAL AND METHODS: Murine cochlear explants and paraffin-embedded cochleae were evaluated with immunohistochemistry for OCT2 and MATE1. Explant cultures were also treated with Texas Red cisplatin to determine their cellular uptake. RESULTS: MATE1 is present in the cochlea. Most intense labeling of MATE1 and OCT2 was seen in the outer hair cells (OHCs) and pillar cells, respectively. Both transporters were observed in the spiral ganglion neurons and stria vascularis. Expression levels of OCT2 and MATE1 decreased following cisplatin exposure. Texas Red cisplatin staining was strong in OHCs and pillar cells. CONCLUSIONS AND SIGNIFICANCE: To the best of our knowledge, this is the first study demonstrating the presence and localization of MATE1 in the cochlea. OCT2 labeling was seen in pillar cells. Consistently, OHCs and pillar cells uptake Texas Red cisplatin.
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Cisplatino , Ototoxicidade , Camundongos , Animais , Cisplatino/toxicidade , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Cóclea/metabolismoRESUMO
Magnetite nanoparticles (NPs) are one of the most investigated nanomaterials so far and modern synthesis methods currently provide an exceptional control of their size, shape, crystallinity and surface functionalization. These advances have enabled their use in different fields ranging from environmental applications to biomedicine. However, several studies have shown that the precise composition and crystal structure of magnetite NPs depend on their redox phase transformations, which have a profound impact on their physicochemical properties and, ultimately, on their technological applications. Although the physical mechanisms behind such chemical transformations in bulk materials have been known for a long time, experiments on NPs with large surface-to-volume ratios have revealed intriguing results. This article is focused on reviewing the current status of the field. Following an introduction on the fundamental properties of magnetite and other related iron oxides (including maghemite and wüstite), some basic concepts on the chemical routes to prepare iron oxide nanomaterials are presented. The key experimental techniques available to study phase transformations in iron oxides, their advantages and drawbacks to the study of nanomaterials are then discussed. The major section of this work is devoted to the topotactic oxidation of magnetite NPs and, in this regard, the cation diffusion model that accounts for the experimental results on the kinetics of the process is critically examined. Since many synthesis routes rely on the formation of monodisperse magnetite NPs via oxidation of wüstite counterparts, the modulation of their physical properties by crystal defects arising from the oxidation process is also described. Finally, the importance of a precise control of the composition and structure of magnetite-based NPs is discussed and its role in their biomedical applications is highlighted.
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Ethyl(hydroxyethyl)cellulose (EHEC) and a silica-based xerogel (SBX) were functionalized with a (18-crown-6)-styrylpyridine precursor (1) to obtain the modified polymers EHEC-1 and SBX-1, respectively. Films were obtained and the resulting materials were used as fluorogenic devices for the detection of Hg2+ in water. The films produced from EHEC-1 showed high water retention, making it difficult to apply as a reusable optical chemosensor. Since SBXs are recognized in the literature for their hydrophobicity, a hybrid film composed of EHEC and SBX-1 which did not show water retention was produced and characterized. This system showed rapid response time, outstanding selectivity compared to several other studied metal ions, and sensitivity for the detection of Hg2+ in water. The detection limit for this material using fluorescence technique was 2 ppb (â¼10-8 mol L-1). The reversibility of the complex formed between EHEC-SBX-1 film and Hg2+ was demonstrated by the addition of cysteine to the medium. The result obtained also allowed the assembly of INHIBIT and IMPLICATION molecular logic gates, using Hg2+ and cysteine as inputs. The results described in this article have important significance in the development of novel reversible fluorogenic chemosensors and adsorbent materials for the effective removal of Hg2+ ions.
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Mercúrio , Água , Cisteína , Dióxido de Silício , Íons , Corantes FluorescentesRESUMO
Chronic Non-Communicable Diseases (NCDs) have been considered a global health problem, characterized as diseases of multiple factors, which are developed throughout life, and regardless of genetics as a risk factor of important relevance, the increase in mortality attributed to the disease to environmental factors and the lifestyle one leads. Although the reactive species (ROS/RNS) are necessary for several physiological processes, their overproduction is directly related to the pathogenesis and aggravation of NCDs. In contrast, dietary polyphenols have been widely associated with minimizing oxidative stress and inflammation. In addition to their antioxidant power, polyphenols have also drawn attention for being able to modulate both gene expression and modify epigenetic alterations, suggesting an essential involvement in the prevention and/or development of some pathologies. Therefore, this review briefly explained the mechanisms in the development of some NCDs, followed by a summary of some evidence related to the interaction of polyphenols in oxidative stress, as well as the modulation of epigenetic mechanisms involved in the management of NCDs.
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Proteínas tirosina-fosfatase (PTPs) possuem papel fundamental na regulação da transdução de sinais e estão envolvidas em diversos processos fundamentais do ciclo celular. As Cdc25 (Cell Division Cycle 25) são fosfatases duais encontradas em todos os organismos eucarióticos e atuam em checkpoints do ciclo celular, permitindo ou inibindo o prosseguimento deste. Este grupo de proteínas pertence à classe de PTPs com atividade baseada em cisteína, apresenta domínio catalítico altamente conservado assim como o motivo catalítico, P-loop. Devido sua função, as Cdc25 são consideradas possíveis alvos terapêuticos para tratamento de câncer e sua interação com pequenas moléculas e inibidores tem sido investigada de forma que análises estruturais e de ligação das Cdc25 com inibidores podem elucidar aspectos importantes do mecanismo de ação destes além de direcionar para o desenho racional de fármacos. Interações cátion-π são interações intra ou intermoleculares não-covalentes que ocorrem entre uma espécie química catiônica, como o grupo guanidino de argininas, e uma das faces de um sistema π rico em elétrons, como dos anéis indólicos de triptofanos. Apesar de pouco discutidas na literatura, quando em comparação às interações não-covalentes mais convencionais, do ponto de vista energético as interações cátion-π são tão importantes na estruturação de proteínas quanto às ligações de hidrogênio ou pontes salinas. De fato estas interações são observadas com frequência em estruturas proteicas resolvidas. O domínio catalítico da Cdc25B possui diversas argininas expostas em sua superfície e um único resíduo de triptofano localizado na região C-terminal flexível, muito próximo do sítio catalítico da proteína. A flexibilidade de proteínas ou de regiões proteicas apresenta importante papel no reconhecimento entre biomoléculas participantes de vias de sinalização e tem sido muito estudada atualmente. Aqui, simulações de dinâmica molecular, experimentos de 1H-15N HSQC RMN, ensaios de cinética de inibição e de ancoragem molecular, evidenciam a existência de contatos cátion-π transientes na superfície de um importante membro da família das Cdc25, a Cdc25B, e de sítios de interação entre inibidores testados e a proteína com destaque a sítios na proximidades do P-loop, região próxima ao C-terminal desordenado, onde se demonstra estabilidade da interação com os pequenos ligantes
Protein tyrosine phosphatase (PTPs) play a fundamental role in the regulation of signal transduction and are involved in several fundamental processes of the cell cycle. Cdc25 (Cell Division Cycle 25) are dual phosphatases found in all eukaryotic organisms and act at checkpoints of the cell cycle, allowing or inhibiting its progression. This group of proteins belongs to the class of PTPs with cysteine-based activity, presenting a highly conserved catalytic domain as well as the catalytic motif, P-loop. Due to their function, Cdc25 are considered possible therapeutic targets for cancer treatment and their interaction with small molecules and inhibitors has been investigated so that structural and binding analyzes of Cdc25 with inhibitors can elucidate important aspects of their mechanism of action besides directing to rational drug design. Cation-π interactions are non-covalent intra- or intermolecular interactions that occur between a cationic chemical species, such as the guanidino group of arginines, and one of the faces of an electron-rich system, such as the indole rings of tryptophans. Although little discussed in the literature, when compared to more conventional non-covalent interactions, from the energetic point of view, cation-π interactions are as important in the structuring of proteins as hydrogen bonds or salt bridges. In fact, these interactions are frequently observed in solved protein structures. The catalytic domain of Cdc25B has several arginines exposed on its surface and a single tryptophan residue located in the flexible C-terminal region, very close to the catalytic site of the protein. The flexibility of proteins or protein regions plays an important role in the recognition between biomolecules participating in signaling pathways and has been extensively studied today. Here, molecular dynamics simulations, 1H-15N HSQC NMR experiments, inhibition kinetics and molecular anchoring assays, evidence the existence of transient cation-π contacts on the surface of an important member of the Cdc25 family, Cdc25B, and of sites of interaction between tested inhibitors and the protein, with emphasis on sites in the vicinity of the P-loop, a region close to the disordered C-terminus, where stability of the interaction with the small ligands is demonstrated
Assuntos
Fosfatases cdc25/análise , Simulação de Acoplamento Molecular/métodos , Simulação de Dinâmica Molecular/classificaçãoRESUMO
Environmental pollutants are today a major concern and an intensely discussed topic on the global agenda for sustainable development. They include a wide range of organic compounds, such as pharmaceutical waste, pesticides, plastics, and volatile organic compounds that can be found in air, soil, water bodies, sewage, and industrial wastewater. In addition to impacting fauna, flora, and fungi, skin absorption, inhalation, and ingestion of some pollutants can also negatively affect human health. Fungi play a crucial role in the decomposition and cycle of natural and synthetic substances. They exhibit a variety of growth, metabolic, morphological, and reproductive strategies and can be found in association with animals, plants, algae, and cyanobacteria. There are fungal strains that occur naturally in soil, sediment, and water that have inherent abilities to survive with contaminants, making the organism important for bioassay applications. In this context, we reviewed the applications of fungal-based bioassays as a versatile tool for environmental monitoring.
RESUMO
The π-complexes of cationic coinage metal ions (Cu(I), Ag(I), Au(I)) provide useful experimental support for understanding fundamental characteristics of bonding and 13 C-NMR patterns of the group 11 triad. Here, we account for the role of relativistic effects on olefin-coinage metal ion interaction for cationic, homoleptic tris-ethylene, and tris-norbornene complexes, [M(η2 -C2 H4 )3 ]+ and [M(η2 -C7 H10 )3 ]+ (M = Cu, Ag, Au), as representative case of studies. The M-(CC) bond strength in the cationic, tris-ethylene complexes is affected sizably for Au and to a lesser extent for Ag and Cu (48.6%, 16.7%, and 4.3%, respectively), owing to the influence on the different stabilizing terms accounting for the interaction energy in the formation of coinage metal cation-π complexes. The bonding elements provided by olefin â M σ-donation and olefin â M π-backbonding are consequently affected, leading to a lesser covalent interaction going down in the triad if the relativistic effects are ignored. Analysis of the 13 C-NMR tensors provides further understanding of the observed experimental values, where the degree of backbonding charge donation to π2 *-olefin orbital is the main influence on the observed high-field shifts in comparison to the free olefin. This donation is larger for ethylene complexes and lower for norbornene counterparts. However, the bonding energy in the later complexes is slightly stabilized given by the enhancement in the electrostatic character of the interaction. Thus, the theoretical evaluation of metal-alkene bonds, and other metal-bonding situations, benefits from the incorporation of relativistic effects even in lighter counterparts, which have an increasing role going down in the group.
RESUMO
Abstract Background Pain is an uncomfortable sensation in the body. Kaempferol is a flavonoid with antinociceptive effects. Transient receptor potential (TRP) channels have been characterized in the sensory system. Objective This study evaluated the central antinociceptive effect of Kaempferol and possible mechanisms of action of transient receptor potential cation channel subfamily V member 1 (TRPV1). Methods Capsaicin as a TRPV agonist (5 μg/μL, intracerebroventricular [ICV]) and capsazepine as its antagonist (10 μg/μL, icv) were used to test the analgesic effect of kaempferol (1.5 mg, ICV). Morphine (10 μg, ICV) was used as a positive control. The other groups were treated with a combination of kaempferol and capsaicin, kaempferol and capsazepine, and capsaicin and capsazepine. The cannula was implanted in the cerebroventricular area. The tail-flick, acetic acid, and formalin tests were used to assess analgesic activity.For evaluation of antiinflammatory effect, the formalin-induced rat pawedema was used. Results Kaempferol significantly decreased pain in the acute pain models, including the tail-flick and the first phase of the formalin test. In the late phase of the formalin test, as a valid model of nociception, capsazepine inhibited the antinociceptive effect of kaempferol. Conclusions Kaempferol has an analgesic effect in the acute pain model and can affect inflammatory pain. Also, the TRPV1 channel plays a role in the antinociceptive activity of kaempferol.
Resumo Antecedentes A dor é uma sensação desconfortável no corpo. Kaempferol é um flavonoide com efeitos antinociceptivos. Canais receptores de potencial transitório têm sido caracterizados no sistema sensorial. Objetivo Este estudo avaliou o efeito antinociceptivo central do kaempferol e os possíveis mecanismos de ação do TRPV1. Métodos Capsaicina como agonista de TRPV (5 μg/μL, intracerebroventricular [ICV]) e capsazepina como seu antagonista (10 μg/μL, icv) foram usados para testar o efeito analgésico do kaempferol (1,5 mg, ICV). A morfina (10 μg, ICV) foi usada como controle positivo. Os outros grupos foram tratados com uma combinação de kaempferol e capsaicina, kaempferol e capsazepina e capsaicina e capsazepina. A cânula foi implantada na área cerebroventricular. Os testes de movimento de cauda, ácido acético e formalina foram usados para avaliar a atividade analgésica. Para avaliação do efeito anti-inflamatório, foi utilizado o edema de pata de rato induzido por formalina. Resultados Kaempferol diminuiu significativamente a dor nos modelos de dor aguda, incluindo o movimento da cauda e a primeira fase do teste de formalina. Na fase tardia do teste da formalina, como modelo válido de nocicepção, a capsazepina inibiu o efeito antinociceptivo do kaempferol. Conclusões Kaempferol tem efeito analgésico no modelo de dor aguda e pode afetar a dor inflamatória. Além disso, o canal TRPV1 desempenha um papel na atividade antinociceptiva do kaempferol.
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Cancer is a complex pathology of great heterogeneity and difficulty that makes the constant search for new therapies necessary. A major advance on the subject has been made by focusing on the development of new drugs aimed to alter the metabolism of cancer cells, by generating a disruption of mitochondrial function. For this purpose, several new compounds with specific mitochondrial action have been tested, leading successfully to cell death. Recently, attention has centered on a group of natural compounds present in plants named polyphenols, among which is caffeic acid, a polyphenol that has proven to be a powerful antitumoral agent and a prominent compound for studies focused on the development of new therapies against cancer.In this review, we revised the antitumoral capacity and mechanisms of action of caffeic acid and its derivatives, with special emphasis in a new class of caffeic acid derivatives that target mitochondria by chemical binding to the lipophilic cation triphenylphosphonium.
Assuntos
Mitocôndrias , Neoplasias , Humanos , Mitocôndrias/metabolismo , Ácidos Cafeicos/química , Ácidos Cafeicos/metabolismo , Ácidos Cafeicos/farmacologia , Neoplasias/metabolismo , Antioxidantes/farmacologia , Polifenóis/farmacologiaRESUMO
Resumen En el presente trabajo, el aporte al conocimiento de las orquídeas del Perú que realizó Augusto Weberbauer en su obra El mundo vegetal de los Andes peruanos es analizado. Durante sus estudios botánicos, Weberbauer recolectó alrededor de 264 ejemplares de orquídeas, los cuales no sólo sirvieron para enriquecer su obra; sino también sirvió para que otros botánicos describieran nuevas especies de orquídeas. También, se presenta una relación de los ejemplares de Weberbauer depositados en diferentes herbarios; agrupados en cuatro listados: 1) material tipo con ejemplares en colecciones de herbario, 2) material tipo sin ejemplares existentes en colecciones de herbario, 3) material no tipo en colecciones de herbario y 4) material no tipo citado en la literatura; y se designan lectotipos para 70 nombres de Orchidaceae.
Abstract In the present work, the contribution to the knowledge of the orchids of Peru that Augusto Weberbauer made in his work El mundo vegetal de los Andes peruanos is analyzed. During his botanical studies, Weberbauer collected about 264 specimens of orchids, which not only served to enrich his work; but also served for other botanists to describe new species of orchids. Also, a list of the specimens of Weberbauer deposited in different herbariums is presented; grouped into four lists: 1) type material with specimens in herbarium collections, 2) type material without existing specimens in herbarium collections, 3) non-type material in herbarium collections, and 4) non-type material cited in the literature; and lectotypes are designated for 70 Orchidaceae names.