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1.
Chemosphere ; 341: 139927, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37633614

RESUMEN

Recently, much attention has been focused on the application of the Ionic Liquids (ILs) with herbicidal activity in agriculture. It has been suggested that through the appropriate selection of cations and anions, one can adjust the properties of ILs, particularly the hydrophobicity, solubility, bioavailability, toxicity. In practical agricultural conditions, it will be beneficial to reduce the mobility of herbicidal anions, such as the commonly applied 2,4-dichlorophenoxyacetic acid [2,4-D] in the soil. Furthermore, microplastics are becoming increasingly prevalent in the soil, potentially stimulating herbicidal sorption. Therefore, we investigated whether cations in ILs influence the mobility of anions in OECD soil supplemented with polystyrene microplastic (PS). For this purpose, we used the 2,4-D based ILs consisting of: a hydrophilic choline cation [Chol][2,4-D] and a hydrophobic choline cation with a C12chain [C12Chol][2,4-D]. Characterization of selected micropolystyrene was carried out using the BET sorption-desorption isotherm, particle size distribution and changes in soil sorption parameters such as soil sorption capacity and cation exchange capacity. Based on the batch sorption experiment, the effect of microplastic on the sorption of individual cations and anions in soil contaminated with micropolystyrene was evaluated. The results obtained indicate that the introduction of a 1-10% (w/w) PS resulted in an 18-23% increase of the soil sorption capacity. However, the sorption of both ILs' cations increased only by 3-5%. No sorption of the [2,4-D] anion was noted. This suggests that cations and anions forming ILs, behave independently of each other in the environment. The results indicate the fact that ILs upon introduction into the environment are not a new type of emerging contaminant, but rather a typical mixture of ions. It is worth noting that when analyzing the behavior of ILs in the environment, it is necessary to follow the fate of both cations and anions.


Asunto(s)
Herbicidas , Líquidos Iónicos , Microplásticos , Plásticos , Líquidos Iónicos/química , Poliestirenos , Suelo/química , Aniones , Herbicidas/química , Cationes/química , Colina , Ácido 2,4-Diclorofenoxiacético
2.
J Hazard Mater ; 443(Pt A): 130171, 2023 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-36367467

RESUMEN

Despite the fact that rhamnolipids are among the most studied biosurfactants, there are still several gaps which must be filled. The aim of this review is to emphasize and to indicate which issues should be taken into account in order to achieve efficient rhamnolipids-assisted biodegradation or phytoextraction of soils contaminated by heavy metals and petroleum hydrocarbons without harmful side effects. Four main topics have been elucidated in the review: effective concentration of rhamnolipids in soil, their potential phytotoxicity, susceptibility to biodegradation and interaction with soil microorganisms. The discussed elements are often closely associated and often overlap, thus making the interpretation of research results all the more challenging. Each dedicated section of this review includes a description of potential issues and questions, an explanation of the background and rationale for each problem, analysis of relevant literature reports and a short summary with possible application guidelines. The main conclusion is that there is a necessity to establish regulations regarding effective concentrations for rhamnolipids-assisted remediation of soil. The use of an improper concentration is the direct cause of all the other discussed phenomena.


Asunto(s)
Metales Pesados , Petróleo , Contaminantes del Suelo , Petróleo/metabolismo , Suelo , Contaminantes del Suelo/metabolismo , Metales Pesados/toxicidad , Metales Pesados/análisis , Hidrocarburos/análisis , Biodegradación Ambiental , Microbiología del Suelo
3.
Bull Math Biol ; 83(10): 105, 2021 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-34477982

RESUMEN

We formulate a multiscale mathematical model that describes the bioreduction of uranium in porous media. On the mesoscale we describe the bioreduction of uranium [VI] to uranium [IV] using a multispecies one-dimensional biofilm model with suspended bacteria and thermodynamic growth inhibition. We upscale the mesoscopic (colony scale) model to the macroscale (reactor scale) and investigate the behavior of substrate utilization and production, attachment and detachment processes, and thermodynamic effects not usually considered in biofilm growth models. Simulation results of the reactor model indicate that thermodynamic inhibition quantitatively alters the dynamics of the model and neglecting thermodynamic effects may over- or underestimate chemical concentrations in the system. Furthermore, we numerically investigate uncertainties related to the specific choice of attachment and detachment rate coefficients and find that while increasing the attachment rate coefficient or decreasing the detachment rate coefficient leads to thicker biofilms, performance of the reactor remains largely unaffected.


Asunto(s)
Uranio , Biopelículas , Reactores Biológicos , Medios de Cultivo , Conceptos Matemáticos , Porosidad
4.
Front Bioeng Biotechnol ; 8: 572892, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33195133

RESUMEN

Rhamnolipids are among the glycolipids that have been investigated intensively in the last decades, mostly produced by the facultative pathogen Pseudomonas aeruginosa using plant oils as carbon source and antifoam agent. Simplification of downstream processing is envisaged using hydrophilic carbon sources, such as glucose, employing recombinant non-pathogenic Pseudomonas putida KT2440 for rhamnolipid or 3-(3-hydroxyalkanoyloxy)alkanoic acid (HAA, i.e., rhamnolipid precursors) production. However, during scale-up of the cultivation from shake flask to bioreactor, excessive foam formation hinders the use of standard fermentation protocols. In this study, the foam was guided from the reactor to a foam fractionation column to separate biosurfactants from medium and bacterial cells. Applying this integrated unit operation, the space-time yield (STY) for rhamnolipid synthesis could be increased by a factor of 2.8 (STY = 0.17 gRL/L·h) compared to the production in shake flasks. The accumulation of bacteria at the gas-liquid interface of the foam resulted in removal of whole-cell biocatalyst from the reactor with the strong consequence of reduced rhamnolipid production. To diminish the accumulation of bacteria at the gas-liquid interface, we deleted genes encoding cell-surface structures, focusing on hydrophobic proteins present on P. putida KT2440. Strains lacking, e.g., the flagellum, fimbriae, exopolysaccharides, and specific surface proteins, were tested for cell surface hydrophobicity and foam adsorption. Without flagellum or the large adhesion protein F (LapF), foam enrichment of these modified P. putida KT2440 was reduced by 23 and 51%, respectively. In a bioreactor cultivation of the non-motile strain with integrated rhamnolipid production genes, biomass enrichment in the foam was reduced by 46% compared to the reference strain. The intensification of rhamnolipid production from hydrophilic carbon sources presented here is an example for integrated strain and process engineering. This approach will become routine in the development of whole-cell catalysts for the envisaged bioeconomy. The results are discussed in the context of the importance of interacting strain and process engineering early in the development of bioprocesses.

5.
Bull Math Biol ; 82(6): 76, 2020 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-32535693

RESUMEN

We formulate a mathematical model of bacterial populations in a chemostat setting that also accounts for thermodynamic growth inhibition as a consequence of chemical reactions. Using only elementary mathematical and chemical arguments, we carry this out for two systems: a simple toy model with a single species, a single substrate, and a single reaction product, and a more involved model that describes bioreduction of uranium[VI] into uranium[IV]. We find that in contrast to most traditional chemostat models, as a consequence of thermodynamic inhibition the equilibria concentrations of nutrient substrates might depend on their inflow concentration and not only on reaction parameters and the reactor's dilution rate. Simulation results of the uranium degradation model indicate that thermodynamic growth inhibition quantitatively alters the solution of the model. This suggests that neglecting thermodynamic inhibition effects in systems where they play a role might lead to wrong model predictions and under- or over-estimate the efficacy of the process under investigation.


Asunto(s)
Bacterias/crecimiento & desarrollo , Bacterias/metabolismo , Modelos Biológicos , Uranio/farmacocinética , Biodegradación Ambiental , Reactores Biológicos , Biología Computacional , Simulación por Computador , Conceptos Matemáticos , Oxidación-Reducción , Termodinámica , Uranio/química
6.
Molecules ; 25(4)2020 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-32075198

RESUMEN

Crude oil-derived hydrocarbons constitute the largest group of environmental pollutants worldwide. The number of reports concerning their toxicity and emphasizing the ultimate need to remove them from marine and soil environments confirms the unceasing interest of scientists in this field. Among the various techniques used for clean-up actions, bioremediation seems to be the most acceptable and economically justified. Analysis of recent reports regarding unsuccessful bioremediation attempts indicates that there is a need to highlight the fundamental aspects of hydrocarbon microbiology in a clear and concise manner. Therefore, in this review, we would like to elucidate some crucial, but often overlooked, factors. First, the formation of crude oil and abundance of naturally occurring hydrocarbons is presented and compared with bacterial ability to not only survive but also to utilize such compounds as an attractive energy source. Then, the significance of nutrient limitation on biomass growth is underlined on the example of a specially designed experiment and discussed in context of bioremediation efficiency. Next, the formation of aerobic and anaerobic conditions, as well as the role of surfactants for maintaining appropriate C:N:P ratio during initial stages of biodegradation is explained. Finally, a summary of recent scientific reports focused on the removal of hydrocarbon contaminants using bioaugmentation, biostimulation and introduction of surfactants, as well as biosurfactants, is presented. This review was designed to be a comprehensive source of knowledge regarding the unique aspects of hydrocarbon microbiology that may be useful for planning future biodegradation experiments. In addition, it is a starting point for wider debate regarding the limitations and possible improvements of currently employed bioremediation strategies.


Asunto(s)
Bacterias/química , Biodegradación Ambiental , Hidrocarburos/química , Petróleo/toxicidad , Bacterias/metabolismo , Humanos , Hidrocarburos/efectos adversos , Hidrocarburos/toxicidad , Contaminación por Petróleo/prevención & control , Contaminantes del Suelo/química , Tensoactivos/química
7.
Neuroimage ; 208: 116440, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31841682

RESUMEN

Aging impacts both visual short-term memory (vSTM) capacity and thalamo-cortical connectivity. According to the Neural Theory of Visual Attention, vSTM depends on the structural connectivity between posterior thalamus and visual occipital cortices (PT-OC). We tested whether aging modifies the association between vSTM capacity and PT-OC structural connectivity. To do so, 66 individuals aged 20-77 years were assessed by diffusion-weighted imaging used for probabilistic tractography and performed a psychophysical whole-report task of briefly presented letter arrays, from which vSTM capacity estimates were derived. We found reduced vSTM capacity, and aberrant PT-OC connection probability in aging. Critically, age modified the relationship between vSTM capacity and PT-OC connection probability: in younger adults, vSTM capacity was negatively correlated with PT-OC connection probability while in older adults, this association was positive. Furthermore, age modified the microstructure of PT-OC tracts suggesting that the inversion of the association between PT-OC connection probability and vSTM capacity with aging might reflect age-related changes in white-matter properties. Accordingly, our results demonstrate that age-related differences in vSTM capacity links with the microstructure and connectivity of PT-OC tracts.


Asunto(s)
Envejecimiento/patología , Envejecimiento/fisiología , Atención/fisiología , Memoria a Corto Plazo/fisiología , Red Nerviosa/anatomía & histología , Lóbulo Occipital/anatomía & histología , Tálamo/anatomía & histología , Percepción Visual/fisiología , Adulto , Anciano , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Lóbulo Occipital/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Adulto Joven
8.
Neuroimage ; 195: 67-77, 2019 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-30928688

RESUMEN

In the theory of visual attention (TVA), it is suggested that objects in a visual scene compete for representation in a visual short-term memory (vSTM) store. The race towards the store is assumed to be biased by top-down controlled weighting of the objects according to their task relevance. Only objects that reach the store before its capacity limitation is reached are represented consciously in a given instant. TVA-based computational modeling of participants' performance in whole- and partial-report tasks permits independent parameters of individual efficiency of top-down control α and vSTM storage capacity K to be extracted. The neural interpretation of the TVA proposes recurrent loops between the posterior thalamus and posterior visual cortices to be relevant for generating attentional weights for competing objects and for maintaining selected objects in vSTM. Accordingly, we tested whether structural connectivity between posterior thalamus and occipital cortices (PT-OC) is associated with estimates of top-down control and vSTM capacity. We applied whole- and partial-report tasks and probabilistic tractography in a sample of 37 healthy adults. We found vSTM capacity K to be associated with left PT-OC structural connectivity and a trend-wise relation between top-down control α and right PT-OC structural connectivity. These findings support the assumption of the relevance of thalamic structures and their connections to visual cortex for top-down control and vSTM capacity.


Asunto(s)
Atención/fisiología , Memoria a Corto Plazo/fisiología , Lóbulo Occipital/fisiología , Tálamo/fisiología , Adulto , Imagen de Difusión Tensora/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vías Nerviosas/fisiología , Adulto Joven
9.
Molecules ; 23(6)2018 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-29899233

RESUMEN

The marine hydrocarbonoclastic bacterium Alcanivorax borkumensis is well known for its ability to successfully degrade various mixtures of n-alkanes occurring in marine oil spills. For effective growth on these compounds, the bacteria possess the unique capability not only to incorporate but also to modify fatty intermediates derived from the alkane degradation pathway. High efficiency of both these processes provides better competitiveness for a single bacteria species among hydrocarbon degraders. To examine the efficiency of A. borkumensis to cope with different sources of fatty acid intermediates, we studied the growth rates and membrane fatty acid patterns of this bacterium cultivated on diesel, biodiesel and rapeseed oil as carbon and energy source. Obtained results revealed significant differences in both parameters depending on growth substrate. Highest growth rates were observed with biodiesel, while growth rates on rapeseed oil and diesel were lower than on the standard reference compound (hexadecane). The most remarkable observation is that cells grown on rapeseed oil, biodiesel, and diesel showed significant amounts of the two polyunsaturated fatty acids linoleic acid and linolenic acid in their membrane. By direct incorporation of these external fatty acids, the bacteria save energy allowing them to degrade those pollutants in a more efficient way. Such fast adaptation may increase resilience of A. borkumensis and allow them to strive and maintain populations in more complex hydrocarbon degrading microbial communities.


Asunto(s)
Alcanivoraceae/crecimiento & desarrollo , Carbono/metabolismo , Ácidos Grasos/análisis , Lípidos de la Membrana/análisis , Alcanivoraceae/química , Biodegradación Ambiental , Biocombustibles , Membrana Celular/química , Hidrocarburos/metabolismo , Interacciones Hidrofóbicas e Hidrofílicas , Aceite de Brassica napus/química
10.
Osteoporos Int ; 29(10): 2251-2260, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29943190

RESUMEN

Information regarding the prevalence and risk of osteoporosis among American Indian (AI) women is limited. This study showed that with increasing AI blood quantum, the prevalence of osteoporosis at the hip based on BMD T-scores decreased and this appeared to be independent of other risk factors. INTRODUCTION: This study was designed to investigate the effects of AI blood quantum (BQ) on osteoporosis prevalence and risk in a cohort of AI women in Oklahoma. METHODS: Women (n = 301), aged 50 years and older, were recruited to participate in the Oklahoma American Indian Women's Osteoporosis Study. Baseline bone density, fracture history, bone biochemical markers, and potential risk factors were assessed. Participants were stratified by AI BQ into BQ1 ≤ 25%, BQ2 = 25-49%, BQ3 = 50-74%, and BQ4 = 75-100%. The effects of BQ on the prevalence and risk of osteoporosis were evaluated. RESULTS: Based on T-scores, one in approximately eight women in the study was osteoporotic at one or more sites. The prevalence of osteoporosis decreased (p < 0.05) with increasing BQ, especially at the hip, trochanteric, and intertrochanter regions. No differences in bone-specific alkaline phosphatase and C-telopeptide were observed across BQ that could account for the differences in bone density. 25-OH vitamin D decreased with increasing BQ, but mean for each BQ1-4 was > 40 ng/mL. Fracture history did not differ across BQ, and though 52% of the population consumed less than the RDA for calcium, no effect of BQ was observed. CONCLUSIONS: In this cohort of women who identified as AI, greater Indian BQ was associated with a decrease in the prevalence of osteoporosis.


Asunto(s)
Indígenas Norteamericanos/estadística & datos numéricos , Osteoporosis Posmenopáusica/etnología , Anciano , Antropometría/métodos , Composición Corporal/fisiología , Densidad Ósea/fisiología , Calcio de la Dieta/administración & dosificación , Estudios Transversales , Suplementos Dietéticos , Femenino , Humanos , Persona de Mediana Edad , Oklahoma/epidemiología , Osteoporosis Posmenopáusica/fisiopatología , Fracturas Osteoporóticas/etnología , Fracturas Osteoporóticas/fisiopatología , Prevalencia , Medición de Riesgo/métodos
11.
Science ; 360(6390): 743-746, 2018 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-29773745

RESUMEN

Prokaryotes in natural environments respond rapidly to high concentrations of chemicals and physical stresses. Exposure to anthropogenic toxic substances-such as oil, chlorinated solvents, or antibiotics-favors the evolution of resistant phenotypes, some of which can use contaminants as an exclusive carbon source or as electron donors and acceptors. Microorganisms similarly adapt to extreme pH, metal, or osmotic stress. The metabolic plasticity of prokaryotes can thus be harnessed for bioremediation and can be exploited in a variety of ways, ranging from stimulated natural attenuation to bioaugmentation and from wastewater treatment to habitat restoration.


Asunto(s)
Bacterias/metabolismo , Biodegradación Ambiental , Desinfectantes/efectos adversos , Farmacorresistencia Microbiana , Selección Genética , Bacterias/efectos de los fármacos , Bacterias/genética , Desinfectantes/farmacología , Farmacorresistencia Microbiana/genética , Petróleo
12.
SLAS Technol ; 22(3): 315-324, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28376702

RESUMEN

Cystic fibrosis (CF) is a hereditary disease caused by mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). A large number of nearly 2000 reported mutations, including the premature termination codon (PTC) mutations, urgently require new and personalized medicines. We have developed cell-based assays for readthrough modulators of CFTR PTC mutations (or nonsense mutation suppressors), based on the trafficking and surface expression of CFTR. Approximately 85,000 compounds have been screened for two PTC mutations (Y122X and W1282X). The hit rates at the threshold of 50% greater than vehicle response are 2% and 1.4% for CFTR Y122X and CFTR W1282X, respectively. The overlap of the two hit sets at this stringent hit threshold is relatively small. Only ~28% of the hits from the W1282X screen were also hits in the Y122X screen. The overlap increases to ~50% if compounds are included that in the second screen achieve only a less stringent hit criterion, that is, horseradish peroxidase (HRP) activity greater than three standard deviations above the mean of the vehicle. Our data suggest that personalization may not need to address individual genotypes, but that patients with different CFTR PTC mutations could benefit from the same medicines.


Asunto(s)
Codón sin Sentido , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística/tratamiento farmacológico , Evaluación Preclínica de Medicamentos/métodos , Transcripción Genética/efectos de los fármacos , Técnicas Citológicas/métodos , Humanos
13.
Neuroimage ; 150: 68-76, 2017 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-28188917

RESUMEN

Preterm birth is associated with an increased risk for lasting changes in both the cortico-thalamic system and attention; however, the link between cortico-thalamic and attention changes is as yet little understood. In preterm newborns, cortico-cortical and cortico-thalamic structural connectivity are distinctively altered, with increased local clustering for cortico-cortical and decreased integrity for cortico-thalamic connectivity. In preterm-born adults, among the various attention functions, visual short-term memory (vSTM) capacity is selectively impaired. We hypothesized distinct associations between vSTM capacity and the structural integrity of cortico-thalamic and cortico-cortical connections, respectively, in preterm-born adults. A whole-report paradigm of briefly presented letter arrays based on the computationally formalized Theory of Visual Attention (TVA) was used to quantify parameter vSTM capacity in 26 preterm- and 21 full-term-born adults. Fractional anisotropy (FA) of posterior thalamic radiations and the splenium of the corpus callosum obtained by diffusion tensor imaging were analyzed by tract-based spatial statistics and used as proxies for cortico-thalamic and cortico-cortical structural connectivity. The relationship between vSTM capacity and cortico-thalamic and cortico-cortical connectivity, respectively, was significantly modified by prematurity. In full-term-born adults, the higher FA in the right posterior thalamic radiation the higher vSTM capacity; in preterm-born adults this FA-vSTM-relationship was inversed. In the splenium, higher FA was correlated with higher vSTM capacity in preterm-born adults, whereas no significant relationship was evident in full-term-born adults. These results indicate distinct associations between cortico-thalamic and cortico-cortical integrity and vSTM capacity in preterm-and full-term-born adults. Data suggest compensatory cortico-cortical fiber re-organization for attention deficits after preterm delivery.


Asunto(s)
Cuerpo Calloso/patología , Trastornos de la Memoria/patología , Vías Nerviosas/patología , Nacimiento Prematuro/patología , Tálamo/patología , Adulto , Atención/fisiología , Imagen de Difusión Tensora , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Estudios Longitudinales , Masculino , Trastornos de la Memoria/etiología , Memoria a Corto Plazo/fisiología , Embarazo , Percepción Visual/fisiología
14.
Subcell Biochem ; 76: 323-41, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26219718

RESUMEN

Hypophosphatasia (HPP) is a rare monogenetic and multisystemic disease with involvement of different organs, including bone, muscle, kidney, lung, gastrointestinal tract and the nervous system. The exact metabolic mechanisms of the effects of TNAP deficiency in different tissues are not understood in detail. There is no approved specific treatment for HPP; therefore symptomatic treatment in order to improve the clinical features is of major interest. Enzyme replacement therapy (ERT) is a relatively new type of treatment based on the principle of administering a medical treatment replacing a defective or absent enzyme. Recently ERT with a bone targeted recombinant human TNAP molecule has been reported to be efficient in ten severely affected patients and improved survival of life threatening forms. These results are very promising especially with regard to the skeletal phenotype but it is unclear whether ERT also has beneficial effects for craniosynostosis and in other affected tissues in HPP such as brain and kidney. Long-term data are not yet available and further systematic clinical trials are needed. It is also necessary to establish therapeutic approaches to help patients who are affected by less severe forms of HPP but also suffer from a significant reduction in quality of life. Further basic research on TNAP function and role in different tissues and on its physiological substrates is critical to gain a better insight in the pathogenesis in HPP. This and further experiences in new therapeutic strategies may improve the prognosis and quality of life of patients with all forms of HPP.


Asunto(s)
Proteínas Portadoras/genética , Proteínas Portadoras/uso terapéutico , Terapia de Reemplazo Enzimático , Hipofosfatasia/tratamiento farmacológico , Proteínas Recombinantes/uso terapéutico , Fosfatasa Alcalina/administración & dosificación , Fosfatasa Alcalina/uso terapéutico , Animales , Proteínas Portadoras/administración & dosificación , Sistemas de Liberación de Medicamentos , Evaluación Preclínica de Medicamentos , Terapia de Reemplazo Enzimático/métodos , Humanos , Inmunoglobulina G/administración & dosificación , Inmunoglobulina G/uso terapéutico , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/uso terapéutico
15.
PLoS One ; 9(8): e104616, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25101849

RESUMEN

Icariin, a major constituent of flavonoids from the Chinese medicinal herb Epimedium brevicornum, exhibits multiple biological properties, including anti-inflammatory, neuroregulatory and neuroprotective activities. Therefore, Icariin might be applied in treatment of neurodegenerative disorders, including Alzheimer's disease (AD), which is neuropathologically characterized by ß-amyloid aggregation, hyperphosphorylated tau and neuroinflammation. Potential therapeutic effects of Icariin were investigated in an animal model of cerebral amyloidosis for AD, transgenic APP/PS1 mouse. Icariin was suspended in carboxymethylcellulose and given orally to APP/PS1 mice. Therapeutic effects were monitored by behavioral tests, namely nesting assay, before and during the experimental treatment. Following an oral treatment of 10 days, Icariin significantly attenuated Aß deposition, microglial activation and TGF-ß1 immunoreactivity at amyloid plaques in cortex and hippocampus of transgenic mice 5 months of age, and restored impaired nesting ability. Our results suggest that Icariin might be considered a promising therapeutic option for human AD.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Precursor de Proteína beta-Amiloide/biosíntesis , Conducta Animal/efectos de los fármacos , Flavonoides/farmacología , Factor de Crecimiento Transformador beta1/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Precursor de Proteína beta-Amiloide/genética , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Transgénicos , Factor de Crecimiento Transformador beta1/genética
16.
BMC Complement Altern Med ; 13: 254, 2013 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-24089706

RESUMEN

BACKGROUND: Inflammatory response in the CNS mediated by microglia cells play an important role in host defense and is implicated in the pathology of neurodegenerative diseases. We investigated the capacity of Entada africana to protect microglia from inflammatory insults by exploring the effect of the CH2Cl2/MEOH 5% fraction (Ea5) on pro-inflammatory cytokines mRNA expression. Finally, we studied the effect of Ea5 on the inhibition of p38 MAPK Kinase. The results were compared to those obtained with Baicalin, a well reported anti-inflammatory flavonoid. METHODS: Barks from E. africana were harvested in 2010, in the west region of Cameroon. A crude extract was prepared using CH2Cl2/MEOH 1:1 V/V. The crude extract obtained was further fractionated by flash chromatography. A mouse microglia cell line (N9) was stimulated by LPS with or without different concentrations of Baicalin and Ea5. The release of NO was evaluated using the Griess method. The expression of pro-inflammatory cytokines mRNA (TNFα, IL-1ß, IL-6) and iNOS/NO were measured by RT- PCR. The inhibition of p38 MAPK Kinase was assessed using ELISA. RESULTS: We found that Ea5, as well as Baicalin inhibited LPS-induced NO production in a dose dependent manner. Ea5 was most active in term of NO inhibition (87.07%), in comparison to Baicalin (70.85%). The expression of TNFα, IL-1ß, IL-6 and iNOS was strongly suppressed by Ea5 in microglia. Ea5 also inhibited the activity of p38MAPK Kinase, up to 30% for the concentrations tested, whereas a prominent inhibition was obtained with Baicalin. CONCLUSION: These results suggest that E. africana may contain promising compounds useful for the treatment of diseases cause by over-activation of microglia such as Alzheimer disease and other neurological diseases.


Asunto(s)
Citocinas/metabolismo , Fabaceae/química , Expresión Génica/efectos de los fármacos , Microglía/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Extractos Vegetales/farmacología , Análisis de Varianza , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citocinas/genética , Lipopolisacáridos/toxicidad , Metanol , Cloruro de Metileno , Ratones , Microglía/citología , Microglía/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Extractos Vegetales/química , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
17.
J Biol Chem ; 288(40): 29025-34, 2013 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-23943619

RESUMEN

STIM1 and Orai1 represent the two molecular key components of the Ca(2+) release-activated Ca(2+) channels. Their activation involves STIM1 C terminus coupling to both the N terminus and the C terminus of Orai. Here we focused on the extended transmembrane Orai1 N-terminal (ETON, aa73-90) region, conserved among the Orai family forming an elongated helix of TM1 as recently shown by x-ray crystallography. To identify "hot spot" residues in the ETON binding interface for STIM1 interaction, numerous Orai1 constructs with N-terminal truncations or point mutations within the ETON region were generated. N-terminal truncations of the first four residues of the ETON region or beyond completely abolished STIM1-dependent Orai1 function. Loss of Orai1 function resulted from neither an impairment of plasma membrane targeting nor pore damage, but from a disruption of STIM1 interaction. In a complementary approach, we monitored STIM1-Orai interaction via Orai1 V102A by determining restored Ca(2+) selectivity as a consequence of STIM1 coupling. Orai1 N-terminal truncations that led to a loss of function consistently failed to restore Ca(2+) selectivity of Orai1 V102A in the presence of STIM1, demonstrating impairment of STIM1 binding. Hence, the major portion of the ETON region (aa76-90) is essential for STIM1 binding and Orai1 activation. Mutagenesis within the ETON region revealed several hydrophobic and basic hot spot residues that appear to control STIM1 coupling to Orai1 in a concerted manner. Moreover, we identified two basic residues, which protrude into the elongated pore to redound to Orai1 gating. We suggest that several hot spot residues in the ETON region contribute in aggregate to the binding of STIM1, which in turn is coupled to a conformational reorientation of the gate.


Asunto(s)
Canales de Calcio/química , Canales de Calcio/metabolismo , Activación del Canal Iónico , Proteínas de la Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Potenciales de Acción , Secuencia de Aminoácidos , Aminoácidos/metabolismo , Sitios de Unión , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Datos de Secuencia Molecular , Proteínas Mutantes/metabolismo , Proteína ORAI1 , Unión Proteica , Estructura Terciaria de Proteína , Eliminación de Secuencia/genética , Molécula de Interacción Estromal 1 , Relación Estructura-Actividad
18.
J Ethnopharmacol ; 149(1): 162-8, 2013 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-23796875

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Entada africana is a plant used in African traditional medicine for the treatment of stomachache, fever, liver related diseases, wound healing, cataract and dysentery. AIMS OF THE STUDY: This study aimed at evaluating the anti-inflammatory activity of fractions of the stem bark extract of the plant using lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages model. MATERIALS AND METHODS: The crude extract was prepared using the mixture CH2Cl2/MeOH (1:1, v/v) and fractionated by flash chromatography using solvents of increasing polarity to obtain five different fractions. The effects of the fractions on the cells viability were studied by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and their inhibitory activity against LPS-induced nitric oxide (NO) production screened by Griess test. The most active fraction was further investigated for its effects on reactive oxygen species (ROS) production using flux cytometry, the expression of inducible nitric oxide synthase (iNOS), pro-and anti-inflammatory cytokines (IL1ß, TNFα, IL6, IL10 and IL13) by RT-PCR, and the activity of the enzyme p38 MAPK kinase by enzyme-linked immunosorbent assay (ELISA). RESULTS: The fractions presented no significant effect on the viability of macrophages at 100 µg/ml after 24h incubation. The CH2Cl2/MeOH 5% (Ea5) fraction was found to be the most potent in inhibiting NO production with a half inhibition concentration (IC50)=18.36 µg/ml, and showed the highest inhibition percentage (89.068%) in comparison with Baicalin (63.34%), an external standard at 50 µg/ml. Ea5, as well as Baicalin significantly (P<0.05) inhibited the expression of TNFα, IL6 and IL1ß mRNA, attenuated mRNA expression of inducible NO synthase in a concentration-dependent manner, stimulated the expression of anti-inflammatory cytokines (IL10 and IL13), and showed a 30% inhibition of the activity of p38 MAPK kinase. CONCLUSION: The results of the present study indicate that the fraction Ea5 of Entada africana possesses most potent in vitro anti-inflammatory activity and may contain compounds useful as a therapeutic agent in the treatment of inflammatory related diseases cause by over-activation of macrophages.


Asunto(s)
Antiinflamatorios/farmacología , Etnofarmacología , Fabaceae/química , Macrófagos/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citocinas/inmunología , Relación Dosis-Respuesta a Droga , Lipopolisacáridos/farmacología , Macrófagos/inmunología , Macrófagos/patología , Medicinas Tradicionales Africanas , Ratones , Óxido Nítrico/biosíntesis , Corteza de la Planta/química , Extractos Vegetales/aislamiento & purificación , Tallos de la Planta/química , Especies Reactivas de Oxígeno/metabolismo
19.
FEMS Microbiol Lett ; 343(2): 105-12, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23521025

RESUMEN

Four bacterial strains capable of growing in the presence of tannic acid as sole carbon and energy source were isolated from olive mill waste mixtures. 16S rRNA gene sequencing assigned them to the genus Klebsiella. The most efficient strain, Klebsiella sp. strain C2A, was able to degrade 3.5 g L(-1) tannic acid within 35 h with synthesizing gallic acid as main product. The capability of Klebsiella sp. strain C2A to produce tannase was evidenced at high concentrations of tannic acid up to 50 g L(-1) . The bacteria adapted to the toxicity of tannic acids by an increase in the membrane lipid fatty acids degree of saturation, especially in the presence of concentrations higher than 20 g L(-1) . The highly tolerant and adaptable bacterial strain characterized in this study could be used in bioremediation processes of wastes rich in polyphenols such as those derived from olive mills, winery or tanneries.


Asunto(s)
Klebsiella/efectos de los fármacos , Klebsiella/metabolismo , Taninos/metabolismo , Taninos/farmacología , Hidrolasas de Éster Carboxílico/metabolismo , Membrana Celular/metabolismo , Klebsiella/clasificación , Klebsiella/genética , Klebsiella/aislamiento & purificación , Datos de Secuencia Molecular , Aceite de Oliva , Fosfolípidos/metabolismo , Filogenia , Aceites de Plantas , ARN Bacteriano , ARN Ribosómico 16S , Residuos
20.
Environ Toxicol Pharmacol ; 33(2): 135-40, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22209725

RESUMEN

The environmental agent aluminum has been extensively investigated for a potential relationship with amyloid precursor protein (APP) expression. Despite many investigations, there is at present no definite proof from which to draw a conclusion. Since APP is an integral membrane protein expressed in different tissues and capable of fluxes across the blood-brain barrier (BBB), which may ultimately affect APP level in brain, it is necessary to assess the expression profile among vital body organs. The present study compared aluminum oxide and aluminum chloride injected rats with control rats (saline treated) to observe if aluminum affected APP expression patterns in different organs by immunohistochemistry (IHC). The expression of APP was observed in the brain of aluminum chloride treated rats and in the liver of aluminum oxide injected group. Results of double IHC staining showed that it is Kupffer cells, which are located in liver sinus and expressed APP after aluminum oxide treatment. Oxidative stress is suggested as the potential pathway that aluminum chloride exert effects in brain. These results suggest that different aluminum compounds may impact the expression of APP in brain and liver tissues. The mechanism that aluminum induced liver APP expression still needs further investigation.


Asunto(s)
Compuestos de Aluminio/toxicidad , Óxido de Aluminio/toxicidad , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/efectos de los fármacos , Cloruros/toxicidad , Contaminantes Ambientales/toxicidad , Hígado/efectos de los fármacos , Cloruro de Aluminio , Compuestos de Aluminio/administración & dosificación , Óxido de Aluminio/administración & dosificación , Animales , Encéfalo/metabolismo , Cloruros/administración & dosificación , Colesterol/sangre , Contaminantes Ambientales/administración & dosificación , Inmunohistoquímica , Macrófagos del Hígado/efectos de los fármacos , Macrófagos del Hígado/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley
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